HAEM5:Myelodysplastic neoplasm with low blasts and 5q deletion: Difference between revisions

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Xiaolin Hu, Ph.D; Teresa Smolarek, Ph.D, FACMG

[[File:del(5)(q15q33).png|del(5)(q15q33)|322x322px]]

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|Acceptable

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|Not Recommended

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NA

* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

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|<span class="blue-text">EXAMPLE:</span>

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!Chromosomal Pattern

!Molecular Pathogenesis

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|<span class="blue-text">EXAMPLE:</span>

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The most characteristic cytogenetic abnormality is an interstitial deletion on the long arm of chromosome 5 or del(5q)<ref name=":0">{{Cite journal|last=Van Den Berghe|first=Herman|last2=Cassiman|first2=Jean-Jacques|last3=David|first3=Guido|last4=Fryns|first4=Jean-Pierre|last5=Michaux|first5=Jean-Louis|last6=Sokal|first6=Gerard|date=1974|title=Distinct haematological disorder with deletion of long arm of No. 5 chromosome|url=http://www.nature.com/articles/251437a0|journal=Nature|language=en|volume=251|issue=5474|pages=437–438|doi=10.1038/251437a0|issn=0028-0836}}</ref>  The break point is not fixed but the region between bands q31 and q33 is generally deleted. Several candidates genes were thought to contribute to the haploinsufficiency effect of the deleted region, including ''RPS14'' <ref>{{Cite journal|last=Ebert|first=Benjamin L.|last2=Pretz|first2=Jennifer|last3=Bosco|first3=Jocelyn|last4=Chang|first4=Cindy Y.|last5=Tamayo|first5=Pablo|last6=Galili|first6=Naomi|last7=Raza|first7=Azra|last8=Root|first8=David E.|last9=Attar|first9=Eyal|date=2008|title=Identification of RPS14 as a 5q- syndrome gene by RNA interference screen|url=http://www.nature.com/articles/nature06494|journal=Nature|language=en|volume=451|issue=7176|pages=335–339|doi=10.1038/nature06494|issn=0028-0836|pmc=PMC3771855|pmid=18202658}}</ref>'', CSNK1A1'' <ref name=":1">{{Cite journal|last=Schneider|first=Rebekka K.|last2=Ademà|first2=Vera|last3=Heckl|first3=Dirk|last4=Järås|first4=Marcus|last5=Mallo|first5=Mar|last6=Lord|first6=Allegra M.|last7=Chu|first7=Lisa P.|last8=McConkey|first8=Marie E.|last9=Kramann|first9=Rafael|date=2014|title=Role of Casein Kinase 1A1 in the Biology and Targeted Therapy of del(5q) MDS|url=https://linkinghub.elsevier.com/retrieve/pii/S1535610814003353|journal=Cancer Cell|language=en|volume=26|issue=4|pages=509–520|doi=10.1016/j.ccr.2014.08.001|pmc=PMC4199102|pmid=25242043}}</ref>'','' miR-145 and miR-146a <ref>{{Cite journal|last=Starczynowski|first=Daniel T|last2=Kuchenbauer|first2=Florian|last3=Argiropoulos|first3=Bob|last4=Sung|first4=Sandy|last5=Morin|first5=Ryan|last6=Muranyi|first6=Andrew|last7=Hirst|first7=Martin|last8=Hogge|first8=Donna|last9=Marra|first9=Marco|date=2010|title=Identification of miR-145 and miR-146a as mediators of the 5q– syndrome phenotype|url=http://www.nature.com/articles/nm.2054|journal=Nature Medicine|language=en|volume=16|issue=1|pages=49–58|doi=10.1038/nm.2054|issn=1078-8956}}</ref>. Identification of del(5q) has clinical significance because patients with this cytogenetic abnormality have a good prognosis and they respond well to lenalidomide treatment.     

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|<span class="blue-text">EXAMPLE:</span>''EGFR''

|}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.

Somatic mutations in ''JAK2'' and ''MPL'' have been reported in a small subset patients with isolated del(5q), but these mutations seem not confer diagnostic or prognostic value <ref>{{Cite journal|last=Patnaik|first=M M|last2=Lasho|first2=T L|last3=Finke|first3=C M|last4=Gangat|first4=N|last5=Caramazza|first5=D|last6=Holtan|first6=S G|last7=Pardanani|first7=A|last8=Knudson|first8=R A|last9=Ketterling|first9=R P|date=2010|title=WHO-defined ‘myelodysplastic syndrome with isolated del(5q)’ in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations|url=http://www.nature.com/articles/leu2010105|journal=Leukemia|language=en|volume=24|issue=7|pages=1283–1289|doi=10.1038/leu.2010.105|issn=0887-6924|pmc=PMC3035970|pmid=20485371}}</ref>. A subset of cases could have ''[[SF3B1]]'' mutations, which needs to be differentiated with MDS-RS.

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Several candidate genes in the common deleted region of 5q have been reported to contribute to the molecular pathogenesis.

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==Notes==

          

<nowiki>*</nowiki>''Citation of this Page'': “Myelodysplastic neoplasm with low blasts and 5q deletion”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myelodysplastic_neoplasm_with_low_blasts_and_5q_deletion</nowiki>.