Compendium of Cancer Genome Aberrations

HAEM5:B-lymphoblastic leukaemia/lymphoma with high hyperdiploidy: Difference between revisions

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{{DISPLAYTITLE:B-lymphoblastic leukaemia/lymphoma with high hyperdiploidy}}
{{DISPLAYTITLE:B-lymphoblastic leukaemia/lymphoma with high hyperdiploidy}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


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==Primary Author(s)*==
==Primary Author(s)*==


Afia Hasnain, MBBS, PhD; Yassmine Akkari, PhD, FACMG
Miguel Gonzalez Mancera, MD
==WHO Classification of Disease==
==WHO Classification of Disease==


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==Gene Rearrangements==
==Gene Rearrangements==


No recurrent gene rearrangements have been described<ref name=":3" />.


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
Line 57: Line 59:
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
| ||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|<span class="blue-text">EXAMPLE:</span>
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
|-
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<span class="blue-text">EXAMPLE:</span> D
|
|
|<span class="blue-text">EXAMPLE:</span>
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|
|<span class="blue-text">EXAMPLE:</span>
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|
|
|
|-
|-
|
|
|
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|
|
|
|
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* Gene Mutations (SNV/INDEL)}}</blockquote>
* Gene Mutations (SNV/INDEL)}}</blockquote>


*Pediatric patients with high hyperdiploidy have been reported to have a favorable prognosis with cure seen in >90% of children <ref>{{Cite journal|last=Paulsson|first=Kajsa|last2=Forestier|first2=Erik|last3=Andersen|first3=Mette K.|last4=Autio|first4=Kirsi|last5=Barbany|first5=Gisela|last6=Borgström|first6=Georg|last7=Cavelier|first7=Lucia|last8=Golovleva|first8=Irina|last9=Heim|first9=Sverre|date=2013-09|title=High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols|url=https://pubmed.ncbi.nlm.nih.gov/23645689|journal=Haematologica|volume=98|issue=9|pages=1424–1432|doi=10.3324/haematol.2013.085852|issn=1592-8721|pmc=3762100|pmid=23645689}}</ref>
*Pediatric patients with high hyperdiploidy have been reported to have a favorable prognosis with cure seen in >90% of children <ref name=":0">{{Cite journal|last=Paulsson|first=Kajsa|last2=Forestier|first2=Erik|last3=Andersen|first3=Mette K.|last4=Autio|first4=Kirsi|last5=Barbany|first5=Gisela|last6=Borgström|first6=Georg|last7=Cavelier|first7=Lucia|last8=Golovleva|first8=Irina|last9=Heim|first9=Sverre|date=2013-09|title=High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols|url=https://pubmed.ncbi.nlm.nih.gov/23645689|journal=Haematologica|volume=98|issue=9|pages=1424–1432|doi=10.3324/haematol.2013.085852|issn=1592-8721|pmc=3762100|pmid=23645689}}</ref>
*High event-free survival (EFS) was associated with trisomy 4, 6, 17, 18, and 22, presence of triple trisomies (4, 10, 17), and high modal numbers ( > 50 chromosomes) <ref>{{Cite journal|last=Paulsson|first=Kajsa|last2=Forestier|first2=Erik|last3=Andersen|first3=Mette K.|last4=Autio|first4=Kirsi|last5=Barbany|first5=Gisela|last6=Borgström|first6=Georg|last7=Cavelier|first7=Lucia|last8=Golovleva|first8=Irina|last9=Heim|first9=Sverre|date=2013-09|title=High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols|url=https://pubmed.ncbi.nlm.nih.gov/23645689|journal=Haematologica|volume=98|issue=9|pages=1424–1432|doi=10.3324/haematol.2013.085852|issn=1592-8721|pmc=3762100|pmid=23645689}}</ref>
*High event-free survival (EFS) was associated with trisomy 4, 6, 17, 18, and 22, presence of triple trisomies (4, 10, 17), and high modal numbers ( > 50 chromosomes)<ref name=":0" />  
*Negative prognostic features include > 10 years of age, male gender, and bone marrow fibrosis <ref>{{Cite journal|last=Paulsson|first=Kajsa|last2=Forestier|first2=Erik|last3=Andersen|first3=Mette K.|last4=Autio|first4=Kirsi|last5=Barbany|first5=Gisela|last6=Borgström|first6=Georg|last7=Cavelier|first7=Lucia|last8=Golovleva|first8=Irina|last9=Heim|first9=Sverre|date=2013-09|title=High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols|url=https://pubmed.ncbi.nlm.nih.gov/23645689|journal=Haematologica|volume=98|issue=9|pages=1424–1432|doi=10.3324/haematol.2013.085852|issn=1592-8721|pmc=3762100|pmid=23645689}}</ref>
*Negative prognostic features include > 10 years of age, male gender, and bone marrow fibrosis <ref name=":0" />
*Patients with low hyperdiploidy have been reported to have a 49% EFS at 5 years compared to those with high hyperdiploidy with a five-year EFS of 71% <ref>{{Cite journal|last=Chessels|first=J. M.|last2=Swansbury|first2=G. J.|last3=Reeves|first3=B.|last4=Bailey|first4=C. C.|last5=Richards|first5=S. M.|date=1997-10|title=Cytogenetics and prognosis in childhood lymphoblastic leukaemia: results of MRC UKALL X. Medical Research Council Working Party in Childhood Leukaemia|url=https://pubmed.ncbi.nlm.nih.gov/9359508|journal=British Journal of Haematology|volume=99|issue=1|pages=93–100|doi=10.1046/j.1365-2141.1997.3493163.x|issn=0007-1048|pmid=9359508}}</ref>
*Patients with low hyperdiploidy have been reported to have a 49% EFS at 5 years compared to those with high hyperdiploidy with a five-year EFS of 71% <ref>{{Cite journal|last=Chessels|first=J. M.|last2=Swansbury|first2=G. J.|last3=Reeves|first3=B.|last4=Bailey|first4=C. C.|last5=Richards|first5=S. M.|date=1997-10|title=Cytogenetics and prognosis in childhood lymphoblastic leukaemia: results of MRC UKALL X. Medical Research Council Working Party in Childhood Leukaemia|url=https://pubmed.ncbi.nlm.nih.gov/9359508|journal=British Journal of Haematology|volume=99|issue=1|pages=93–100|doi=10.1046/j.1365-2141.1997.3493163.x|issn=0007-1048|pmid=9359508}}</ref>
*Familial Forms
*Familial Forms
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==Individual Region Genomic Gain/Loss/LOH==
==Individual Region Genomic Gain/Loss/LOH==


 
This entity is defined by a hyperdiploid pattern with recurrent, non-random gains of one or more copies of entire chromosomes. Below are the typical chromosomal gains described.
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|21
7
|Gain
|<span class="blue-text">EXAMPLE:</span> Loss
|Chr21
|<span class="blue-text">EXAMPLE:</span>
|''RUNX1''
chr7
|No established significance
|<span class="blue-text">EXAMPLE:</span>
|No
Unknown
|Chromosome 21 is universally gained in high-hyperdiploid B-ALL/LBL <ref>{{Cite journal|last=Harrison|first=Christine J.|last2=Haas|first2=Oskar|last3=Harbott|first3=Jochen|last4=Biondi|first4=Andrea|last5=Stanulla|first5=Martin|last6=Trka|first6=Jan|last7=Izraeli|first7=Shai|last8=Biology and Diagnosis Committee of International Berlin-Frankfürt-Münster study group|date=2010-10|title=Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the Biology and Diagnosis Committee of the International Berlin-Frankfürt-Münster study group|url=https://pubmed.ncbi.nlm.nih.gov/20701601|journal=British Journal of Haematology|volume=151|issue=2|pages=132–142|doi=10.1111/j.1365-2141.2010.08314.x|issn=1365-2141|pmid=20701601}}</ref>; therefore, the presence of multiple (three to five) discrete ''RUNX1'' signals seen when using ''ETV6''::''RUNX1'' FISH probes suggests the presence of high hyperdiploidy.
|<span class="blue-text">EXAMPLE:</span> D, P
|-
|<span class="blue-text">EXAMPLE:</span> No
|X
|<span class="blue-text">EXAMPLE:</span>
|Gain
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
|ChrX
|None
|No established significance
|No
|N/A
|-
|6
|Gain
|Chr6
|None
|No established significance
|No
|N/A
|-
|14
|Gain
|Chr14
|None
|No established significance
|No
|N/A
|-
|18
|Gain
|Chr18
|None
|Prognostic significance: has been correlated with a lower risk of relapse<ref name=":1">{{Cite journal|last=Moorman|first=Anthony V.|last2=Ensor|first2=Hannah M.|last3=Richards|first3=Sue M.|last4=Chilton|first4=Lucy|last5=Schwab|first5=Claire|last6=Kinsey|first6=Sally E.|last7=Vora|first7=Ajay|last8=Mitchell|first8=Chris D.|last9=Harrison|first9=Christine J.|date=2010-05|title=Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial|url=https://pubmed.ncbi.nlm.nih.gov/20409752|journal=The Lancet. Oncology|volume=11|issue=5|pages=429–438|doi=10.1016/S1470-2045(10)70066-8|issn=1474-5488|pmid=20409752}}</ref>.
|No
|N/A
|-
|4
|Gain
|Chr4
|None
|The prognostic impact of the “triple trisomies”, i.e., concurrent rent +4, +10, and +17, is debated; they have been reported to be associated with low risk by the Children’s Oncology Group (COG)<ref>{{Cite journal|last=Schultz|first=Kirk R.|last2=Pullen|first2=D. Jeanette|last3=Sather|first3=Harland N.|last4=Shuster|first4=Jonathan J.|last5=Devidas|first5=Meenakshi|last6=Borowitz|first6=Michael J.|last7=Carroll|first7=Andrew J.|last8=Heerema|first8=Nyla A.|last9=Rubnitz|first9=Jeffrey E.|date=2007-02-01|title=Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG)|url=https://pubmed.ncbi.nlm.nih.gov/17003380|journal=Blood|volume=109|issue=3|pages=926–935|doi=10.1182/blood-2006-01-024729|issn=0006-4971|pmc=1785141|pmid=17003380}}</ref>, but not in UK trials<ref name=":1" />.
|No
|N/A
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|17
8
|Gain
|<span class="blue-text">EXAMPLE:</span> Gain
|Chr17
|<span class="blue-text">EXAMPLE:</span>
|None
chr8
|''See prognosis section for +4 above''
|<span class="blue-text">EXAMPLE:</span>
|No
Unknown
|N/A
|<span class="blue-text">EXAMPLE:</span> D, P
|
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add references).
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|10
17
|Gain
|<span class="blue-text">EXAMPLE:</span> Amp
|Chr10
|<span class="blue-text">EXAMPLE:</span>
|None
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|''See prognosis section for +4 above''
|<span class="blue-text">EXAMPLE:</span>
|No
''ERBB2''
|N/A
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|<span class="blue-text">EXAMPLE:</span>
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
|-
|-
|
|8
|
|Gain
|
|Chr8
|
|None
|
|No established significance
|
|No
|
|N/A
|}
|}


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**8 (38%)
**8 (38%)


<ref>{{Cite journal|last=Paulsson|first=Kajsa|last2=Forestier|first2=Erik|last3=Andersen|first3=Mette K.|last4=Autio|first4=Kirsi|last5=Barbany|first5=Gisela|last6=Borgström|first6=Georg|last7=Cavelier|first7=Lucia|last8=Golovleva|first8=Irina|last9=Heim|first9=Sverre|date=2013-09|title=High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols|url=https://pubmed.ncbi.nlm.nih.gov/23645689|journal=Haematologica|volume=98|issue=9|pages=1424–1432|doi=10.3324/haematol.2013.085852|issn=1592-8721|pmc=3762100|pmid=23645689}}</ref> <ref>{{Cite journal|last=Paulsson|first=Kajsa|last2=Forestier|first2=Erik|last3=Lilljebjörn|first3=Henrik|last4=Heldrup|first4=Jesper|last5=Behrendtz|first5=Mikael|last6=Young|first6=Bryan D.|last7=Johansson|first7=Bertil|date=2010-12-14|title=Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/21098271|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=107|issue=50|pages=21719–21724|doi=10.1073/pnas.1006981107|issn=1091-6490|pmc=3003126|pmid=21098271}}</ref> <ref>{{Cite journal|last=Paulsson|first=Kajsa|last2=Johansson|first2=Bertil|date=2009-08|title=High hyperdiploid childhood acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/19415723|journal=Genes, Chromosomes & Cancer|volume=48|issue=8|pages=637–660|doi=10.1002/gcc.20671|issn=1098-2264|pmid=19415723}}</ref>
<ref name=":0" /> <ref name=":4">{{Cite journal|last=Paulsson|first=Kajsa|last2=Forestier|first2=Erik|last3=Lilljebjörn|first3=Henrik|last4=Heldrup|first4=Jesper|last5=Behrendtz|first5=Mikael|last6=Young|first6=Bryan D.|last7=Johansson|first7=Bertil|date=2010-12-14|title=Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/21098271|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=107|issue=50|pages=21719–21724|doi=10.1073/pnas.1006981107|issn=1091-6490|pmc=3003126|pmid=21098271}}</ref> <ref name=":5">{{Cite journal|last=Paulsson|first=Kajsa|last2=Johansson|first2=Bertil|date=2009-08|title=High hyperdiploid childhood acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/19415723|journal=Genes, Chromosomes & Cancer|volume=48|issue=8|pages=637–660|doi=10.1002/gcc.20671|issn=1098-2264|pmid=19415723}}</ref>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|Hyperdiploid
Co-deletion of 1p and 18q
|Although pathogenetic mechanisms are poorly understood, chromosomal gains are early events in the pathogenesis of B-ALL/LBL with high hyperdiploidy and are the main driver<ref name=":3">WHO Classification of Tumours: Haematolymphoid Tumours [Internet; Beta Version Ahead of Print]
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
 
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
(5th ed.), International Agency for Research on Cancer (2022)
|<span class="blue-text">EXAMPLE:</span> D, P
 
|
<nowiki>https://tumourclassification.iarc.who.int/chapters/63</nowiki></ref>.
|
|-
|<span class="blue-text">EXAMPLE:</span>
Microsatellite instability - hypermutated
|
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
|
|
|-
|
|
|
|
|
|
|
|D: Needs demonstration of high-hyperdiploidy status (comprising 51–65 chromosomes) by karyotyping and/or FISH
P: B-ALL/LBL with high-hyperdiploidy has a very favorable prognosis, with long-term overall survival in > 90% of children
T: N/A
|No
|Pediatric patients with high hyperdiploidy have been reported to have a favorable prognosis with cure seen in >90% of children<ref name=":0" />.
Negative prognostic features include > 10 years of age, male gender, and bone marrow fibrosis<ref name=":0" />.
More recent studies have validated a risk profile determining that outcome appears to be linked to  specific chromosomal gains<ref>{{Cite journal|last=Enshaei|first=Amir|last2=Vora|first2=Ajay|last3=Harrison|first3=Christine J.|last4=Moppett|first4=John|last5=Moorman|first5=Anthony V.|date=2021-11|title=Defining low-risk high hyperdiploidy in patients with paediatric acute lymphoblastic leukaemia: a retrospective analysis of data from the UKALL97/99 and UKALL2003 clinical trials|url=https://pubmed.ncbi.nlm.nih.gov/34715050|journal=The Lancet. Haematology|volume=8|issue=11|pages=e828–e839|doi=10.1016/S2352-3026(21)00304-5|issn=2352-3026|pmc=8567211|pmid=34715050}}</ref>.
|}
|}


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==Gene Mutations (SNV/INDEL)==
==Gene Mutations (SNV/INDEL)==


 
Nine genes have been found to be recurrently mutated and were also either mutated more frequently than expected by chance or targeted by structural events<ref name=":4" />.
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
Line 268: Line 256:
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
|''KRAS''


<br />
<br />
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|Nonsynonymous single nucleotide variant (SNV) in known codon 12 and 13 hotspot region, and additional mutations in codons 116 and 146<ref name=":5" />
|<span class="blue-text">EXAMPLE:</span> Oncogene
|Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|Common
|<span class="blue-text">EXAMPLE:</span> T
|No
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|No
|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
|''KRAS'' codons 117 and 146 may be new recurrent mutational hotspots in high hyperdiploid ALL.
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
|''NRAS''
<br />
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|Nonsynonymous SNV
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|Recurrent
|<span class="blue-text">EXAMPLE:</span> P
|No
|
|No
|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
|N/A
|-
|''FLT3''
|Nonsynonymous SNV, nonframeshift insertion, nonframeshift deletion, nonframeshift substitution
|Tyrosine kinase receptor
|Recurrent
|No
|No
|N/A
|-
|''PTPN11''
|Nonsynonymous SNV
|Protein tyrosine phosphatase
|Recurrent
|No
|No
|N/A
|-
|''CREBBP''
|Nonsynonymous SNV, frameshift insertion, splice site
|Histone acetyltransferase
|Recurrent
|No
|No
|''CREBBP'' has been reported to be mutated in a high proportion of relapsing high hyperdiploid childhood ALLs<ref>{{Cite journal|last=Inthal|first=A.|last2=Zeitlhofer|first2=P.|last3=Zeginigg|first3=M.|last4=Morak|first4=M.|last5=Grausenburger|first5=R.|last6=Fronkova|first6=E.|last7=Fahrner|first7=B.|last8=Mann|first8=G.|last9=Haas|first9=O. A.|date=2012-08|title=CREBBP HAT domain mutations prevail in relapse cases of high hyperdiploid childhood acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/22388726|journal=Leukemia|volume=26|issue=8|pages=1797–1803|doi=10.1038/leu.2012.60|issn=1476-5551|pmc=4194312|pmid=22388726}}</ref>.
|-
|''WHSC1''
|Nonsynonymous SNV
|Histone methyltransferase
|Recurrent
|No
|No
|N/A
|-
|''SUV420H1''
|Nonsynonymous SNV
|Histone methyltransferase
|Rare
|No
|No
|N/A
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|''SETD2''
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|Frameshift insertion
|<span class="blue-text">EXAMPLE:</span> Oncogene
|Histone methyltransferase
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|Rare
|<span class="blue-text">EXAMPLE:</span> T
|No
|
|No
|
|N/A
|-
|-
|
|''EZH2''
|
|Nonsynonymous SNV
|
|Histone methyltransferase
|
|Rarre
|
|No
|
|No
|
|N/A
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
==Epigenomic Alterations==
==Epigenomic Alterations==


 
No relevant epigenomic alterations have been described.
Put your text here
Put your text here
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==
Line 315: Line 343:
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|''FLT3, NRAS, KRAS'' and ''PTPN11''<ref name=":2">{{Cite journal|last=Paulsson|first=Kajsa|last2=Lilljebjörn|first2=Henrik|last3=Biloglav|first3=Andrea|last4=Olsson|first4=Linda|last5=Rissler|first5=Marianne|last6=Castor|first6=Anders|last7=Barbany|first7=Gisela|last8=Fogelstrand|first8=Linda|last9=Nordgren|first9=Ann|date=2015-06|title=The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/25961940|journal=Nature Genetics|volume=47|issue=6|pages=672–676|doi=10.1038/ng.3301|issn=1546-1718|pmid=25961940}}</ref>; Activating mutations
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|Receptor tyrosine kinase (RTK)-RAS signaling
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|Increased proliferation, differentiation, and survival
|-
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|-
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
|-
|
|
|
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
Line 335: Line 351:
Hyperdiploidy is readily identifiable by conventional chromosome studies, FISH and CMA. CMA studies have shown that approximately 80% of hyperdiploid cases have additional genomic abnormalities with chromosomes commonly involved being 1, 9, 11, 12, and X.  
Hyperdiploidy is readily identifiable by conventional chromosome studies, FISH and CMA. CMA studies have shown that approximately 80% of hyperdiploid cases have additional genomic abnormalities with chromosomes commonly involved being 1, 9, 11, 12, and X.  


<ref>{{Cite journal|last=Paulsson|first=Kajsa|last2=Forestier|first2=Erik|last3=Lilljebjörn|first3=Henrik|last4=Heldrup|first4=Jesper|last5=Behrendtz|first5=Mikael|last6=Young|first6=Bryan D.|last7=Johansson|first7=Bertil|date=2010-12-14|title=Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/21098271|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=107|issue=50|pages=21719–21724|doi=10.1073/pnas.1006981107|issn=1091-6490|pmc=3003126|pmid=21098271}}</ref> <ref>{{Cite journal|last=Schraders|first=Margit|last2=van Reijmersdal|first2=Simon V.|last3=Kamping|first3=Eveline J.|last4=van Krieken|first4=Johan H. J. M.|last5=van Kessel|first5=Ad Geurts|last6=Groenen|first6=Patricia J. T. A.|last7=Hoogerbrugge|first7=Peter M.|last8=Kuiper|first8=Roland P.|date=2009-05|title=High-resolution genomic profiling of pediatric lymphoblastic lymphomas reveals subtle differences with pediatric acute lymphoblastic leukemias in the B-lineage|url=https://pubmed.ncbi.nlm.nih.gov/19389505|journal=Cancer Genetics and Cytogenetics|volume=191|issue=1|pages=27–33|doi=10.1016/j.cancergencyto.2009.01.002|issn=1873-4456|pmid=19389505}}</ref><ref>{{Cite journal|last=Steeghs|first=Elisabeth M. P.|last2=Boer|first2=Judith M.|last3=Hoogkamer|first3=Alex Q.|last4=Boeree|first4=Aurélie|last5=de Haas|first5=Valerie|last6=de Groot-Kruseman|first6=Hester A.|last7=Horstmann|first7=Martin A.|last8=Escherich|first8=Gabriele|last9=Pieters|first9=Rob|date=03 15, 2019|title=Copy number alterations in B-cell development genes, drug resistance, and clinical outcome in pediatric B-cell precursor acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/30874617|journal=Scientific Reports|volume=9|issue=1|pages=4634|doi=10.1038/s41598-019-41078-4|issn=2045-2322|pmc=6420659|pmid=30874617}}</ref><ref>{{Cite journal|last=Lejman|first=Monika|last2=Zawitkowska|first2=Joanna|last3=Styka|first3=Borys|last4=Babicz|first4=Mariusz|last5=Winnicka|first5=Dorota|last6=Zaucha-Prażmo|first6=Agnieszka|last7=Pastorczak|first7=Agata|last8=Taha|first8=Joanna|last9=Młynarski|first9=Wojciech|date=08 2019|title=Microarray testing as an efficient tool to redefine hyperdiploid paediatric B-cell precursor acute lymphoblastic leukaemia patients|url=https://pubmed.ncbi.nlm.nih.gov/31202078|journal=Leukemia Research|volume=83|pages=106163|doi=10.1016/j.leukres.2019.05.013|issn=1873-5835|pmid=31202078}}</ref>
<ref name=":4" /> <ref>{{Cite journal|last=Schraders|first=Margit|last2=van Reijmersdal|first2=Simon V.|last3=Kamping|first3=Eveline J.|last4=van Krieken|first4=Johan H. J. M.|last5=van Kessel|first5=Ad Geurts|last6=Groenen|first6=Patricia J. T. A.|last7=Hoogerbrugge|first7=Peter M.|last8=Kuiper|first8=Roland P.|date=2009-05|title=High-resolution genomic profiling of pediatric lymphoblastic lymphomas reveals subtle differences with pediatric acute lymphoblastic leukemias in the B-lineage|url=https://pubmed.ncbi.nlm.nih.gov/19389505|journal=Cancer Genetics and Cytogenetics|volume=191|issue=1|pages=27–33|doi=10.1016/j.cancergencyto.2009.01.002|issn=1873-4456|pmid=19389505}}</ref><ref>{{Cite journal|last=Steeghs|first=Elisabeth M. P.|last2=Boer|first2=Judith M.|last3=Hoogkamer|first3=Alex Q.|last4=Boeree|first4=Aurélie|last5=de Haas|first5=Valerie|last6=de Groot-Kruseman|first6=Hester A.|last7=Horstmann|first7=Martin A.|last8=Escherich|first8=Gabriele|last9=Pieters|first9=Rob|date=03 15, 2019|title=Copy number alterations in B-cell development genes, drug resistance, and clinical outcome in pediatric B-cell precursor acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/30874617|journal=Scientific Reports|volume=9|issue=1|pages=4634|doi=10.1038/s41598-019-41078-4|issn=2045-2322|pmc=6420659|pmid=30874617}}</ref><ref>{{Cite journal|last=Lejman|first=Monika|last2=Zawitkowska|first2=Joanna|last3=Styka|first3=Borys|last4=Babicz|first4=Mariusz|last5=Winnicka|first5=Dorota|last6=Zaucha-Prażmo|first6=Agnieszka|last7=Pastorczak|first7=Agata|last8=Taha|first8=Joanna|last9=Młynarski|first9=Wojciech|date=08 2019|title=Microarray testing as an efficient tool to redefine hyperdiploid paediatric B-cell precursor acute lymphoblastic leukaemia patients|url=https://pubmed.ncbi.nlm.nih.gov/31202078|journal=Leukemia Research|volume=83|pages=106163|doi=10.1016/j.leukres.2019.05.013|issn=1873-5835|pmid=31202078}}</ref>


==Familial Forms==
==Familial Forms==


 
No familial forms have been described.
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
==Additional Information==
==Additional Information==
Retrieved from "https://test.ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_high_hyperdiploidy"