A Heritable Missense Polymorphism in CDKN2A Confers Strong Risk of Childhood Acute Lymphoblastic Leukemia and Is Preferentially Selected during Clonal Evolution

A Heritable Missense Polymorphism in CDKN2A Confers Strong Risk of Childhood Acute Lymphoblastic Leukemia and Is Preferentially Selected during Clonal Evolution

Walsh,K (2015) Cancer Research   (Link to abstract)                                                     



There is an increased interest in heritable genetic variants and their association with cancer. Recent GWAS studies identified SNPs that modify ALL risk; in this study, the authors identify a CDKN2A missense variant that confers 3-fold increase in ALL risk in children of different ethnic backgrounds. The risk was even higher for CDKN2A-deleted ALL. Their findings show that leukemia cells preferentially retain the germline heritable genetic variation, suggesting that it confers a growth advantage. Further somatic loss of the protective CDKN2A allele is commonly observed, demonstrating a direct interaction between heritable and somatic genetic variation in CDKN2A in leukemogenesis.


* This is supportive evidence that there are hereditable genetic changes that raise the risk for developing ALL – another puzzle piece when trying to understand the etiology of this disease. Heritable and somatic alterations in CDKN2A are important for ALL etiology and progression.