Tumor-Specific Mutations More Common in High-Grade Neuroendocrine Tumors

Tumor-specific mutations are common in high-grade neuroendocrine tumors, according to a small single-institution study (NET Abstract #BT13) presented at the 7^th Annual Neuroendocrine Tumors (NET) conference in Nashville, TN. The meeting was organized by the North American Neuroendocrine Tumors Society (NANETS).

“Many of these may guide future therapies and participation in clinical trials,” reported lead study author Namrata Vijayvergia, MD, of the Fox Chase Cancer Center in Philadelphia, PA, and colleagues.

A total of 32 patients at Fox Chase Cancer Center who were diagnosed with advanced-stage NETs of all grades during October 2013 through May 2014 were enrolled in a prospective next-generation sequencing platform protocol to detect somatic mutations in 50 cancer-related genes in primary and metastatic tumor tissue.

Twelve of the 32 patients were found to have tumors harboring tumor-specific mutations. Ki-67 scoring was reviewed for 18 of 32 tumors.

Only “a minority” of low-grade NETS (defined as Ki-67 ≤ 20%) harbored tumor-specific mutations. Of 14 patients with low-grade tumors (Ki-67 > 20%), four (30%) were mutation-positive, compared with all four high-grade NETs that had tumor-specific mutations, Dr. Vijayvergia and coauthors reported.

High-grade tumors harbored BRAF/TP53/PIK3CA, BRAF, TP53, and KRAS/TP53 mutations.

Overall, for tumors of all grades, mutations in tumors of the same primary site varied and overlapped with those of other primary sites. For example, four of 14 NETs of the small or large bowel were found to be mutation-positive, with each of the four harboring a distinct mutation (BRAF, PIK3CA, TP53, and KRAS). Five of 12 pancreatic NETs harbored KRAS (n=2), TP53, RB1, and ATM mutations, and NETs of other primary sites harbored tumor-specific TP53 (n=2) and CTNNB1 mutations.

“NETs are rare, making clinical trial accrual challenging,” Dr. Vijayvergia and colleagues said. Given the few available approved therapies, a better understanding of these tumors’ molecular biology can help with the development of new treatments and assignment of patients to clinical trials, they noted.

Enrollment in the protocol continues at Fox Chase Cancer Center, the authors reported. “Collaborations between centers may help to identify trends in a larger population,” they noted.