Multiple Gene Mutations Predict Recurrence in Malignant Melanoma and Clinical Outcomes, Study Suggests

Multiple Gene Mutations Predict Recurrence in Malignant Melanoma and Clinical Outcomes, Study Suggests

In a new study, researchers investigated whether molecular profiling could predict clinical outcomes, and found that patients with primary malignant melanoma are at a higher risk of recurrent disease if they present mutations in two or more cancer-related genes. The study’s results were recently presented at the 2016 HemOnc Today Melanoma and Cutaneous Malignancies meeting.

Patient molecular profiling has led to significant advancements in the development of new therapeutic strategies, such as BRAF, MEK, PD-1 and CTLA-4 inhibitors. The profiling has also provided clinicians with valuable prognostic data, which is essential for treatment of patients with difficult-to-treat advanced-stage or recurrent malignant melanoma.

In this new study, Francis Si Wai Zih, M.D., MSc, from the department of surgical oncology at Fox Chase Cancer Center, and his colleagues analyzed, through next-generation sequencing, tissue samples from 108 patients with malignant melanoma, in the search for mutations in specific regions where 50 genes are known to be cancer-related. Forty-nine of these patients had recurrent melanoma, 24 patients had distant metastases, and 15 patients had in-transit disease.

In the median 12-month follow-up, researchers reported that 45.3 percent of the patients (49 patients) presented no evidence of the disease, 32.4 percent (35) were alive with the disease, 17.5 percent (19) had died of malignant melanoma, and 2 patients (1.8 percent) had died of other unspecified causes. Sequencing results indicate the identification of 170 mutations in 35 unique genes. Among these, commonly affected genes included NRAS (35 patients), TP53 (23), BRAF V600 (25), and CDKN2A (14).

Of the analyzed patients, 15 (13.8 percent) presented no mutations, 52 patients (48.1 percent) had one mutation, and 41 patients (37.9 percent) harbored two or more mutations. Sixty-one patients had primary tumor samples available for next-generation analysis, and 51 had adequate follow-up data available. In this subgroup, researchers reported a disease-free survival (DFS) of 18 months and 29 percent (12 patients) experienced disease recurrence. Importantly, patients harboring two or more mutations showed a significantly decreased DFS.

In light of these results, researchers suggested that “future studies assess the correlation between mutation status and response to adjuvant therapy, as well as compare the mutational patterns between primary tumors and subsequent metastases or recurrence.”

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