Moriyama T (2015) Lancet Oncology (Link to abstract)
This study looked to identify ALL predisposition variants in ETV6 and to determine how these contribute to the overall risk of childhood ALL. The authors undertook targeted sequencing of ETV6 in 4405 children from COG and St Jude Children's Research Hospital front-line ALL trials with available germline DNA. They compared ETV6 variant genotypes with non-ALL controls to define ALL-related germline risk. They identified 31 exonic variants (four non-sense, 21 missense, one splice site, and five frameshift variants) that were potentially related to ALL risk in 35 cases (1%). These children were significantly older at diagnosis and more likely to be hyperdiploid. 48% of the variants clustered in the erythroblast transformation specific domain and were predicted to be highly deleterious.
* Germline ETV6 variations can predispose to childhood ALL and should be looked for in families with several cases of ALL; recommendations for treatment and surveillance need to be developed.