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 |
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