Germline deletion of ETV6 in familial acute lymphoblastic leukemia Journal Article


Authors: Rampersaud, E.; Ziegler, D. S.; Iacobucci, I.; Payne-Turner, D.; Churchman, M. L.; Schrader, K. A.; Joseph, V.; Offit, K.; Tucker, K.; Sutton, R.; Warby, M.; Chenevix-Trench, G.; Huntsman, D. G.; Tsoli, M.; Scott Mead, R.; Qu, C.; Leventaki, V.; Wu, G.; Mullighan, C. G.
Article Title: Germline deletion of ETV6 in familial acute lymphoblastic leukemia
Abstract: Recent studies have identified germline mutations in TP53, PAX5, ETV6, and IKZF1 in kindreds with familial acute lymphoblastic leukemia (ALL), but the genetic basis of ALL in many kindreds is unknown despite mutational analysis of the exome. Here, we report a germline deletion of ETV6 identified by linkage and structural variant analysis of whole-genome sequencing data segregating in a kindred with thrombocytopenia, B-progenitor acute lymphoblastic leukemia, and diffuse large B-cell lymphoma. The 75-nt deletion removed the ETV6 exon 7 splice acceptor, resulting in exon skipping and protein truncation. The ETV6 deletion was also identified by optimal structural variant analysis of exome sequencing data. These findings identify a new mechanism of germline predisposition in ALL and implicate ETV6 germline variation in predisposition to lymphoma. Importantly, these data highlight the importance of germline structural variant analysis in the search for germline variants predisposing to familial leukemia. © 2019 by The American Society of Hematology
Keywords: adult; controlled study; aged; major clinical study; exon; gene deletion; cancer recurrence; familial disease; thrombocytopenia; genetic variability; acute lymphoblastic leukemia; genetic predisposition; genetic linkage; gene structure; aplastic anemia; b cell leukemia; germline mutation; diffuse large b cell lymphoma; human; male; female; priority journal; article; whole genome sequencing; whole exome sequencing; etv6 gene
Journal Title: Blood Advances
Volume: 3
Issue: 7
ISSN: 2473-9529
Publisher: American Society of Hematology  
Date Published: 2019-04-09
Start Page: 1039
End Page: 1046
Language: English
DOI: 10.1182/bloodadvances.2018030635
PUBMED: 30940639
PROVIDER: scopus
PMCID: PMC6457220
DOI/URL:
Notes: Article -- Export Date: 2 August 2019 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Kenneth Offit
    538 Offit
  2. Vijai Joseph
    126 Joseph