Early onset Merkel cell carcinoma patients could have genetic markers for other cancers

Key takeaways:

• Genetic variants for inheritable cancers were more likely among patients diagnosed with Merkel cell carcinoma (MCC) before age 50 years.
• Genetic testing and counseling are advised for those with early onset MCC.

Many patients with early onset Merkel cell carcinoma have genetic variants leading to possible increased cancer risks and should receive genetic counseling and testing, according to a study.

“Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with approximately 3,000 U.S. cases per year,” Noreen Mohsin, MD, of the NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases, and colleagues wrote. “Understanding the etiology of MCC is crucial to improving treatments and prevention. Because patients with germline cancer predispositions often develop cancer at younger ages, we set out to determine whether patients with early-onset MCC harbor germline cancer risk variants.”

Researchers conducted a case-control analyses of 1,012 subjects including 37 with early onset MCC — defined as patients aged younger than 50 years — 45 patients with later onset MCC and 930 controls who were enrolled in the National Institute of Allergy and Infectious Disease (NIAID) Centralized Sequencing Program and did not have MCC.

Those in the early onset group had Merkel cell polyomavirus (MCPyV) testing and genome sequencing completed on their blood samples. Genome sequencing was also conducted on samples from both the late onset and control groups.

Three curated gene lists were used in genetic analysis, including genes associated with inborn errors of immunity, nuclear DNA repair genes and hereditary cancer genes.

Of 26 patients who completed the MCPyV testing, 25 were positive. Seven of the 37 (19%) subjects in the early onset group had genetic variants associated with cancer predisposition including MAGT1, ATM, BRCA1, BRCA2 and TP53, which have shown genetic predispositions for lymphoma and breast and ovarian cancers. Germline disease variants were also present in nine (1%) of those in the control group, but in zero of those in the late-onset group.

DNA repair gene variants were identified in 19 patients, although the researchers said it was unclear if these gene variants contributed to MCC risk.

“To our knowledge, this is the first study to identify potential heritable risk factors for MCC. We discovered that 19% of patients with early-onset MCC were associated with variants in cancer predisposition syndrome genes,” the authors wrote. “Accordingly, genetic counseling and cascade testing of potentially affected family members should be considered for patients diagnosed with MCC at age younger than 50 years, with a focus on detecting pathogenic variants in ATM, BRCA1, BRCA2, TP53, MAGT1 or DNA repair genes.”