BRCA2 Mutations in Patients With Pediatric Lymphoma

Mutations in the BRCA family of genes are known to predispose patients to a number of solid tumors, including breast, ovarian, and prostate cancers. Mutations in BRCA genes are often transferred via familial inheritance, but they can also arise spontaneously. In an analysis of cancer risk among survivors of childhood cancer from the St Jude Lifetime study, BRCA2 mutations were found to occur frequently among survivors of childhood cancer, particularly non-Hodgkin lymphoma (NHL), increasing the risk of subsequent cancer in these patients. To further evaluate the incidence of BRCA2 mutation among survivors of childhood lymphoma, a study published recently in JAMA Oncology evaluated whole genome sequencing results from 1380 survivors of pediatric or adolescent lymphoma and compared results to cancer-free adults.

The study included survivors of both NHL (n = 565) and Hodgkin lymphoma (HL; n = 810). A total of 13 HL survivors (0.6%) carried pathogenic or likely pathogenic mutations in BRCA2, while similar mutations were found in 8 NHL survivors (1.4%). Median age at lymphoma diagnosis did not impact rates of BRCA2 mutations. Comparison to healthy controls revealed a significant association between lymphoma and BRCA2 mutations in survivors of NHL, but not survivors of HL, with NHL survivors being 5 times more likely to carry BRCA2 mutations than healthy controls. Six of the 8 BRCA2-positive NHL survivors had family histories of BRCA2-associated cancers.

The investigators concluded that the increased risk of NHL among BRCA2 mutation carriers supports the inclusion of NHL as a BRCA-associated tumor and indicated that genetic counseling and BRCA2 mutation testing should be offered to survivors of pediatric and adolescent NHL in an attempt to identify patients at higher risk of developing subsequent cancers. Further studies will be necessary to clarify the link between BRCA2 mutations and childhood lymphoma.

JAMA Oncology. 2019 July 25. [Epub ahead of print.]

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