HAEM5:Myeloid/lymphoid neoplasms with other tyrosine kinase fusion genes: Difference between revisions

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 {{DISPLAYTITLE:Myeloid/lymphoid neoplasms with other tyrosine kinase fusion genes}}
 [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
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 |}
-==WHO Essential and Desirable Genetic Diagnostic Criteria==
-<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
-{| class="wikitable"
-|+
-|WHO Essential Criteria (Genetics)*
-|Detection of a tyrosine kinase fusion gene not classified under specific unique entities (''PDGFRA, PDGFRB, FGFR1, JAK2, FLT3, ETV6::ABL1'')
-|-
-|WHO Desirable Criteria (Genetics)*
-|
-|-
-|Other Classification
-|
-|}
-<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
 ==Related Terminology==
-<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
 {| class="wikitable"
 |+
 |Acceptable
-|
+|N/A
 |-
 |Not Recommended
-|
+|Myeloid/lymphoid neoplasms with tyrosine kinase fusion genes (NOS)
 |}
@@ Line 68: / Line 53: @@
 !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)
+|''FGFR2''||''ETV6::FGFR2'' <ref>{{Cite journal|last=Carll|first=Timothy|last2=Patel|first2=Anand|last3=Derman|first3=Benjamin|last4=Hyjek|first4=Elizabeth|last5=Lager|first5=Angela|last6=Wanjari|first6=Pankhuri|last7=Segal|first7=Jeremy|last8=Odenike|first8=Olatoyosi|last9=Fidai|first9=Shiraz|date=2020-10-13|title=Diagnosis and treatment of mixed phenotype (T-myeloid/lymphoid) acute leukemia with novel ETV6-FGFR2 rearrangement|url=https://pubmed.ncbi.nlm.nih.gov/33049052|journal=Blood Advances|volume=4|issue=19|pages=4924–4928|doi=10.1182/bloodadvances.2019001282|issn=2473-9537|pmc=7556145|pmid=33049052}}</ref>||Fusion between exon 4 of ''ETV6'' and exon 5 of ''FGFR2'' (5′ to 3′ orientation).||Cryptic rearrangement detected by FISH involving chromosomes 10 and 12
-|<span class="blue-text">EXAMPLE:</span> Common (CML)
+|Rare < 5%
-|<span class="blue-text">EXAMPLE:</span> D, P, T
+|D, P, T
-|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
+|Yes (WHO)
-|<span class="blue-text">EXAMPLE:</span>
+|Myeloid / lymphoid acute leukemia.  This fusion suggests abnormal ''FGFR2'' expression. Aberrant The ''FGFR2'' activation resulting from ''ETV6::FGFR2'' may respond to ''FGFR1,2,3'' tyrosine kinase inhibitors (TKIs). <ref>{{Cite journal|last=Katoh|first=Masaru|date=2019-02|title=Fibroblast growth factor receptors as treatment targets in clinical oncology|url=https://pubmed.ncbi.nlm.nih.gov/30367139|journal=Nature Reviews. Clinical Oncology|volume=16|issue=2|pages=105–122|doi=10.1038/s41571-018-0115-y|issn=1759-4782|pmid=30367139}}</ref>  This rearrangement exhibited aggressive clinical behavior, demonstrating resistance to both conventional and intensive chemotherapy, as well as allogeneic stem cell transplantation.<ref>{{Cite journal|last=Carll|first=Timothy|last2=Patel|first2=Anand|last3=Derman|first3=Benjamin|last4=Hyjek|first4=Elizabeth|last5=Lager|first5=Angela|last6=Wanjari|first6=Pankhuri|last7=Segal|first7=Jeremy|last8=Odenike|first8=Olatoyosi|last9=Fidai|first9=Shiraz|date=2020-10-13|title=Diagnosis and treatment of mixed phenotype (T-myeloid/lymphoid) acute leukemia with novel ETV6-FGFR2 rearrangement|url=https://pubmed.ncbi.nlm.nih.gov/33049052|journal=Blood Advances|volume=4|issue=19|pages=4924–4928|doi=10.1182/bloodadvances.2019001282|issn=2473-9537|pmc=7556145|pmid=33049052}}</ref> The prognosis remains unclear due to the limited number of cases.
-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).
+|-
+|''LYN''
+|''ETV6::LYN'' <ref>{{Cite journal|last=Telford|first=N.|last2=Alexander|first2=S.|last3=McGinn|first3=O. J.|last4=Williams|first4=M.|last5=Wood|first5=K. M.|last6=Bloor|first6=A.|last7=Saha|first7=V.|date=2016-04-08|title=Myeloproliferative neoplasm with eosinophilia and T-lymphoblastic lymphoma with ETV6-LYN gene fusion|url=https://pubmed.ncbi.nlm.nih.gov/27058227|journal=Blood Cancer Journal|volume=6|issue=4|pages=e412|doi=10.1038/bcj.2016.11|issn=2044-5385|pmc=4855251|pmid=27058227}}</ref><ref>{{Cite journal|last=Ma|first=Edmond S. K.|last2=Wan|first2=Thomas S. K.|last3=Au|first3=Chun Hang|last4=Ho|first4=Dona N.|last5=Ma|first5=Shing Yan|last6=Ng|first6=Margaret H. L.|last7=Chan|first7=Tsun Leung|date=2017-12|title=Next-generation sequencing and molecular cytogenetic characterization of ETV6-LYN fusion due to chromosomes 1, 8 and 12 rearrangement in acute myeloid leukemia|url=https://pubmed.ncbi.nlm.nih.gov/29153093|journal=Cancer Genetics|volume=218-219|pages=15–19|doi=10.1016/j.cancergen.2017.09.001|issn=2210-7762|pmid=29153093}}</ref><ref>{{Cite journal|last=Tanaka|first=H.|last2=Takeuchi|first2=M.|last3=Takeda|first3=Y.|last4=Sakai|first4=S.|last5=Abe|first5=D.|last6=Ohwada|first6=C.|last7=Sakaida|first7=E.|last8=Shimizu|first8=N.|last9=Saito|first9=Y.|date=2010-01|title=Identification of a novel TEL-Lyn fusion gene in primary myelofibrosis|url=https://pubmed.ncbi.nlm.nih.gov/19710703|journal=Leukemia|volume=24|issue=1|pages=197–200|doi=10.1038/leu.2009.167|issn=1476-5551|pmid=19710703}}</ref>
+|Fusion between exon 5 in ''ETV6'' to exon 8 in ''LYN'' (5′ to 3′ orientation to produce an in-frame chimeric fusion)
+|Complex rearrangements involving chromosomes 8 and 12 [e.g. t(8;12)(q12;p13), ins(12;8)(p13;q11q21)]
+|Rare < 5%
+|D. P,T
+|Yes (WHO)
+|Acute myeloid leukemia / primary myelofibrosis/ T-lymphoblastic leukemia. Resistant to intensive chemotherapy or stem cell transplant, the disease progressed rapidly to terminal AML.<ref>{{Cite journal|last=Telford|first=N.|last2=Alexander|first2=S.|last3=McGinn|first3=O. J.|last4=Williams|first4=M.|last5=Wood|first5=K. M.|last6=Bloor|first6=A.|last7=Saha|first7=V.|date=2016-04-08|title=Myeloproliferative neoplasm with eosinophilia and T-lymphoblastic lymphoma with ETV6-LYN gene fusion|url=https://pubmed.ncbi.nlm.nih.gov/27058227|journal=Blood Cancer Journal|volume=6|issue=4|pages=e412|doi=10.1038/bcj.2016.11|issn=2044-5385|pmc=4855251|pmid=27058227}}</ref> Prognosis is not well defined due to the small number of cases.
+|-
+|''NTRK3''
+|''ETV6::NTRK3''<ref>{{Cite journal|last=Reshmi|first=Shalini C.|last2=Harvey|first2=Richard C.|last3=Roberts|first3=Kathryn G.|last4=Stonerock|first4=Eileen|last5=Smith|first5=Amy|last6=Jenkins|first6=Heather|last7=Chen|first7=I.-Ming|last8=Valentine|first8=Marc|last9=Liu|first9=Yu|date=2017-06-22|title=Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's Oncology Group|url=https://pubmed.ncbi.nlm.nih.gov/28408464|journal=Blood|volume=129|issue=25|pages=3352–3361|doi=10.1182/blood-2016-12-758979|issn=1528-0020|pmc=5482101|pmid=28408464}}</ref><ref>{{Cite journal|last=Roberts|first=Kathryn G.|last2=Li|first2=Yongjin|last3=Payne-Turner|first3=Debbie|last4=Harvey|first4=Richard C.|last5=Yang|first5=Yung-Li|last6=Pei|first6=Deqing|last7=McCastlain|first7=Kelly|last8=Ding|first8=Li|last9=Lu|first9=Charles|date=2014-09-11|title=Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/25207766|journal=The New England Journal of Medicine|volume=371|issue=11|pages=1005–1015|doi=10.1056/NEJMoa1403088|issn=1533-4406|pmc=4191900|pmid=25207766}}</ref>
+|Fusion between ''ETV6'' and ''NTRK3'' (5′ to 3′ orientation)
+|t(12;15)(p13;q25)
+|Rare < 5%
+|T
+|Yes (WHO)
+|''ETV6::NTRK3'' is reported in multiple cancers but rare in acute lymphoblastic leukemia.<ref>{{Cite journal|last=Knezevich|first=S. R.|last2=Garnett|first2=M. J.|last3=Pysher|first3=T. J.|last4=Beckwith|first4=J. B.|last5=Grundy|first5=P. E.|last6=Sorensen|first6=P. H.|date=1998-11-15|title=ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma|url=https://pubmed.ncbi.nlm.nih.gov/9823307|journal=Cancer Research|volume=58|issue=22|pages=5046–5048|issn=0008-5472|pmid=9823307}}</ref><ref>{{Cite journal|last=Tognon|first=Cristina|last2=Knezevich|first2=Stevan R.|last3=Huntsman|first3=David|last4=Roskelley|first4=Calvin D.|last5=Melnyk|first5=Natalya|last6=Mathers|first6=Joan A.|last7=Becker|first7=Laurence|last8=Carneiro|first8=Fatima|last9=MacPherson|first9=Nicol|date=2002-11|title=Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma|url=https://pubmed.ncbi.nlm.nih.gov/12450792|journal=Cancer Cell|volume=2|issue=5|pages=367–376|doi=10.1016/s1535-6108(02)00180-0|issn=1535-6108|pmid=12450792}}</ref><ref>{{Cite journal|last=Alessandri|first=A. J.|last2=Knezevich|first2=S. R.|last3=Mathers|first3=J. A.|last4=Schultz|first4=K. R.|last5=Sorensen|first5=P. H.|date=2001-10|title=Absence of t(12;15) associated ETV6-NTRK3 fusion transcripts in pediatric acute leukemias|url=https://pubmed.ncbi.nlm.nih.gov/11568911|journal=Medical and Pediatric Oncology|volume=37|issue=4|pages=415–416|doi=10.1002/mpo.1222|issn=0098-1532|pmid=11568911}}</ref> The ''ETV6::NTRK3'' responded to the ALK inhibitory crizotinib.<ref>{{Cite journal|last=Roberts|first=Kathryn G.|last2=Li|first2=Yongjin|last3=Payne-Turner|first3=Debbie|last4=Harvey|first4=Richard C.|last5=Yang|first5=Yung-Li|last6=Pei|first6=Deqing|last7=McCastlain|first7=Kelly|last8=Ding|first8=Li|last9=Lu|first9=Charles|date=2014-09-11|title=Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/25207766|journal=The New England Journal of Medicine|volume=371|issue=11|pages=1005–1015|doi=10.1056/NEJMoa1403088|issn=1533-4406|pmc=4191900|pmid=25207766}}</ref> Prognosis is not well defined due to the small number of cases.
+|-
+|ALK
+|''RANBP2::ALK''<ref>{{Cite journal|last=Röttgers|first=S.|last2=Gombert|first2=M.|last3=Teigler-Schlegel|first3=A.|last4=Busch|first4=K.|last5=Gamerdinger|first5=U.|last6=Slany|first6=R.|last7=Harbott|first7=J.|last8=Borkhardt|first8=A.|date=2010-06|title=ALK fusion genes in children with atypical myeloproliferative leukemia|url=https://pubmed.ncbi.nlm.nih.gov/20428197|journal=Leukemia|volume=24|issue=6|pages=1197–1200|doi=10.1038/leu.2010.18|issn=1476-5551|pmid=20428197}}</ref><ref>{{Cite journal|last=Lim|first=Ji-Hun|last2=Jang|first2=Seongsoo|last3=Park|first3=Chan-Jeoung|last4=Cho|first4=Young-Uk|last5=Lee|first5=Je-Hwan|last6=Lee|first6=Kyoo-Hyung|last7=Lee|first7=Jin-Ok|last8=Shin|first8=Jong-Yeon|last9=Kim|first9=Jong-Il|date=2014|title=RANBP2-ALK fusion combined with monosomy 7 in acute myelomonocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/24613277|journal=Cancer Genetics|volume=207|issue=1-2|pages=40–45|doi=10.1016/j.cancergen.2013.12.003|issn=2210-7762|pmid=24613277}}</ref>
+|exon 18 of ''RANBP2'' and exon 20 of ''ALK'' (5′ to 3′ orientation).<ref>{{Cite journal|last=Lim|first=Ji-Hun|last2=Jang|first2=Seongsoo|last3=Park|first3=Chan-Jeoung|last4=Cho|first4=Young-Uk|last5=Lee|first5=Je-Hwan|last6=Lee|first6=Kyoo-Hyung|last7=Lee|first7=Jin-Ok|last8=Shin|first8=Jong-Yeon|last9=Kim|first9=Jong-Il|date=2014|title=RANBP2-ALK fusion combined with monosomy 7 in acute myelomonocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/24613277|journal=Cancer Genetics|volume=207|issue=1-2|pages=40–45|doi=10.1016/j.cancergen.2013.12.003|issn=2210-7762|pmid=24613277}}</ref> Leads to constitutive autophosphorylation of ''ALK'' tyrosine kinase and activating downstream signaling.<ref>{{Cite journal|last=Maesako|first=Yoshitomo|last2=Izumi|first2=Kiyotaka|last3=Okamori|first3=Satoshi|last4=Takeoka|first4=Kayo|last5=Kishimori|first5=Chiyuki|last6=Okumura|first6=Atsuko|last7=Honjo|first7=Gen|last8=Akasaka|first8=Takashi|last9=Ohno|first9=Hitoshi|date=2014-02|title=inv(2)(p23q13)/RAN-binding protein 2 (RANBP2)-ALK fusion gene in myeloid leukemia that developed in an elderly woman|url=https://pubmed.ncbi.nlm.nih.gov/24307515|journal=International Journal of Hematology|volume=99|issue=2|pages=202–207|doi=10.1007/s12185-013-1482-x|issn=1865-3774|pmid=24307515}}</ref>
+|inv(2)(p23q13) / t(2;2)(p23;q13)<ref>{{Cite journal|last=Röttgers|first=S.|last2=Gombert|first2=M.|last3=Teigler-Schlegel|first3=A.|last4=Busch|first4=K.|last5=Gamerdinger|first5=U.|last6=Slany|first6=R.|last7=Harbott|first7=J.|last8=Borkhardt|first8=A.|date=2010-06|title=ALK fusion genes in children with atypical myeloproliferative leukemia|url=https://pubmed.ncbi.nlm.nih.gov/20428197|journal=Leukemia|volume=24|issue=6|pages=1197–1200|doi=10.1038/leu.2010.18|issn=1476-5551|pmid=20428197}}</ref> <ref>{{Cite journal|last=Lim|first=Ji-Hun|last2=Jang|first2=Seongsoo|last3=Park|first3=Chan-Jeoung|last4=Cho|first4=Young-Uk|last5=Lee|first5=Je-Hwan|last6=Lee|first6=Kyoo-Hyung|last7=Lee|first7=Jin-Ok|last8=Shin|first8=Jong-Yeon|last9=Kim|first9=Jong-Il|date=2014|title=RANBP2-ALK fusion combined with monosomy 7 in acute myelomonocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/24613277|journal=Cancer Genetics|volume=207|issue=1-2|pages=40–45|doi=10.1016/j.cancergen.2013.12.003|issn=2210-7762|pmid=24613277}}</ref>
+|Rare < 5%
+|D, P, T
+|Yes (WHO)
+|Acute myelomonocytic leukemia/ myeloproliferative leukemia.  Resistant to intensive chemotherapy and allogeneic SCT. Poor clinical outcome.<ref>{{Cite journal|last=Lim|first=Ji-Hun|last2=Jang|first2=Seongsoo|last3=Park|first3=Chan-Jeoung|last4=Cho|first4=Young-Uk|last5=Lee|first5=Je-Hwan|last6=Lee|first6=Kyoo-Hyung|last7=Lee|first7=Jin-Ok|last8=Shin|first8=Jong-Yeon|last9=Kim|first9=Jong-Il|date=2014|title=RANBP2-ALK fusion combined with monosomy 7 in acute myelomonocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/24613277|journal=Cancer Genetics|volume=207|issue=1-2|pages=40–45|doi=10.1016/j.cancergen.2013.12.003|issn=2210-7762|pmid=24613277}}</ref> Prognosis is not well defined due to the small number of cases.
 |-
-|<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''
+''RET''
-Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
+|''BCR::RET''<ref>{{Cite journal|last=Ballerini|first=P.|last2=Struski|first2=S.|last3=Cresson|first3=C.|last4=Prade|first4=N.|last5=Toujani|first5=S.|last6=Deswarte|first6=C.|last7=Dobbelstein|first7=S.|last8=Petit|first8=A.|last9=Lapillonne|first9=H.|date=2012-11|title=RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation|url=https://pubmed.ncbi.nlm.nih.gov/22513837|journal=Leukemia|volume=26|issue=11|pages=2384–2389|doi=10.1038/leu.2012.109|issn=1476-5551|pmid=22513837}}</ref>
-|<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.
+|Fusion between ''BCR'' exon 4 with the ''RET'' exon 12 (5′ to 3′ orientation).<ref>{{Cite journal|last=Ballerini|first=P.|last2=Struski|first2=S.|last3=Cresson|first3=C.|last4=Prade|first4=N.|last5=Toujani|first5=S.|last6=Deswarte|first6=C.|last7=Dobbelstein|first7=S.|last8=Petit|first8=A.|last9=Lapillonne|first9=H.|date=2012-11|title=RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation|url=https://pubmed.ncbi.nlm.nih.gov/22513837|journal=Leukemia|volume=26|issue=11|pages=2384–2389|doi=10.1038/leu.2012.109|issn=1476-5551|pmid=22513837}}</ref> Aberrant expression of the kinase domain.
-|<span class="blue-text">EXAMPLE:</span> N/A
+|t(10;22)(q11;q11)<ref>{{Cite journal|last=Ballerini|first=P.|last2=Struski|first2=S.|last3=Cresson|first3=C.|last4=Prade|first4=N.|last5=Toujani|first5=S.|last6=Deswarte|first6=C.|last7=Dobbelstein|first7=S.|last8=Petit|first8=A.|last9=Lapillonne|first9=H.|date=2012-11|title=RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation|url=https://pubmed.ncbi.nlm.nih.gov/22513837|journal=Leukemia|volume=26|issue=11|pages=2384–2389|doi=10.1038/leu.2012.109|issn=1476-5551|pmid=22513837}}</ref>
-|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
+|Rare <5%
-|<span class="blue-text">EXAMPLE:</span> T
+|D, P, T
+|Yes (WHO)
 |
-|<span class="blue-text">EXAMPLE:</span>
-Both balanced and unbalanced forms are observed by FISH (add references).
+Associated with chronic myelomonocytic leukemia and monocytic differentiation. Sensitive to Sorafenib, an inhibitor to tyrosine kinase activity.<ref>{{Cite journal|last=Ballerini|first=P.|last2=Struski|first2=S.|last3=Cresson|first3=C.|last4=Prade|first4=N.|last5=Toujani|first5=S.|last6=Deswarte|first6=C.|last7=Dobbelstein|first7=S.|last8=Petit|first8=A.|last9=Lapillonne|first9=H.|date=2012-11|title=RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation|url=https://pubmed.ncbi.nlm.nih.gov/22513837|journal=Leukemia|volume=26|issue=11|pages=2384–2389|doi=10.1038/leu.2012.109|issn=1476-5551|pmid=22513837}}</ref> The prognosis not well defined due to the limited number of cases.
+<br />
 |-
-|<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
-|
-|
-|-
-|
-|
-|
-|
-|
-|
-|
 |
+''RET''
+|''FGFR1OP::RET''<ref>{{Cite journal|last=Ballerini|first=P.|last2=Struski|first2=S.|last3=Cresson|first3=C.|last4=Prade|first4=N.|last5=Toujani|first5=S.|last6=Deswarte|first6=C.|last7=Dobbelstein|first7=S.|last8=Petit|first8=A.|last9=Lapillonne|first9=H.|date=2012-11|title=RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation|url=https://pubmed.ncbi.nlm.nih.gov/22513837|journal=Leukemia|volume=26|issue=11|pages=2384–2389|doi=10.1038/leu.2012.109|issn=1476-5551|pmid=22513837}}</ref>
+|Fusion between ''FGFR1OP'' exon 12 with ''RET'' exon 12 (5′ to 3′ orientation).<ref>{{Cite journal|last=Ballerini|first=P.|last2=Struski|first2=S.|last3=Cresson|first3=C.|last4=Prade|first4=N.|last5=Toujani|first5=S.|last6=Deswarte|first6=C.|last7=Dobbelstein|first7=S.|last8=Petit|first8=A.|last9=Lapillonne|first9=H.|date=2012-11|title=RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation|url=https://pubmed.ncbi.nlm.nih.gov/22513837|journal=Leukemia|volume=26|issue=11|pages=2384–2389|doi=10.1038/leu.2012.109|issn=1476-5551|pmid=22513837}}</ref> Abnormal expression of the tyrosine kinase domain.
+|t(6;10)(q27;q11)<ref>{{Cite journal|last=Ballerini|first=P.|last2=Struski|first2=S.|last3=Cresson|first3=C.|last4=Prade|first4=N.|last5=Toujani|first5=S.|last6=Deswarte|first6=C.|last7=Dobbelstein|first7=S.|last8=Petit|first8=A.|last9=Lapillonne|first9=H.|date=2012-11|title=RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation|url=https://pubmed.ncbi.nlm.nih.gov/22513837|journal=Leukemia|volume=26|issue=11|pages=2384–2389|doi=10.1038/leu.2012.109|issn=1476-5551|pmid=22513837}}</ref>
+|Rare <5%
+|D, P, T
+|Yes (WHO)
+|Associated with chronic myelomonocytic leukemia and monocytic differentiation. The prognosis remains unclear due to the limited number of cases.
 |}
 ==Individual Region Genomic Gain/Loss/LOH==
@@ Line 122: / Line 123: @@
 {| class="wikitable sortable"
 |-
-!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''
+!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
-!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
+!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
-!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
-!'''Clinical Relevance Details/Other Notes'''
+!Clinical Relevance Details/Other Notes
 |-
 |<span class="blue-text">EXAMPLE:</span>
@@ Line 177: / Line 178: @@
 !Chromosomal Pattern
 !Molecular Pathogenesis
-!'''Prevalence -'''
+!Prevalence -
-'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
+Common >20%, Recurrent 5-20% or Rare <5% (Disease)
-!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
+!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
-!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
-!'''Clinical Relevance Details/Other Notes'''
+!Clinical Relevance Details/Other Notes
 |-
 |<span class="blue-text">EXAMPLE:</span>
@@ Line 210: / Line 211: @@
 {| class="wikitable sortable"
 |-
-!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''
+!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
-'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
+Common >20%, Recurrent 5-20% or Rare <5% (Disease)
-!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  '''
+!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
-!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
-!'''Clinical Relevance Details/Other Notes'''
+!Clinical Relevance Details/Other Notes
 |-
 |<span class="blue-text">EXAMPLE:</span>''EGFR''
@@ Line 286: / Line 287: @@
 ==References==
-(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span>
+(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span><references />
 ==Notes==