Abstract LB163: Germline pathogenic variants in melanoma patients
Authors: Beitsch Peter , Wernecke Chloe , Bontempo Kelly , Bentley Brenna , Whitworth Pat , Patel Rakesh 
Published: June 2022

Background: The etiology of melanoma has generally been thought to be exposure to UV radiation (sun and sun tanning lamps). However, the percent of melanoma patients harboring a germline PV is not well studied so we undertook this study to determine the number of patients with melanoma who have a PV.

Methods: Patient data was obtained from the Informed Genetically Annotated Patient (iGAP) Registry, an IRB-approved multi-center longitudinal, observational study designed to capture genetic test results and the patient’s outcome over time. A sequential series of unselected melanoma patients presenting to a single surgical oncologist’s office for treatment underwent multigene panel testing. Additionally, patients who had already undergone multigene panel testing for another reason (breast cancer) were included. The cohort was analyzed overall and in two subgroups: melanoma patients who also had a history of breast cancer and melanoma patients who have never had breast cancer. Demographics collected include age at diagnosis, race, other cancers, stage of melanoma, and thickness of melanoma.

Results: There were 170 patients, most were Caucasian (one Black, one Asian) and the average age was 60.9 years. There were 11 patients with a history of prior melanoma. There were 39 males and 131 females. Stages ranged from zero to four with a majority of them stage one. Average thickness was 2.1 mm. The overall group (170 patients) had 29 (17.06%) with a PV (one patient with melanoma and breast cancer had three PVs). The following table lists the PVs (see Table 1). There were 56 patients with melanoma and breast cancer, eight (14.3%) of which had a PV. In the melanoma without breast cancer group (n = 114), had 21 (17.5%) had a PV.

Conclusions: The cost of germline genetic testing with large panels has fallen precipitously making testing more available for many cancer patients. There have been attempts to define a group of factors in patients with melanoma who should be offered germline testing but with mixed results. Our cohort of melanoma patients (with or without breast cancer) has a PV rate of 17% suggesting that all patients with melanoma should be offered germline genetic testing. Guidelines restricting testing are no longer justified.

Table 1. Melanoma PVs Melanoma without Breast Cancer PVs Melanoma with Breast Cancer PVs MUTYH-Monoallelic 3 BLM 2 CHEK2/1100delC 3 ATM 1 NTHL1 2 BRCA1 1 CDKN2A/p16 2 CHEK2 1 SDHA 2 CHEK2/1100delC 1 ATM 2 MITF 1 MITF 2 MUTYH-Biallelic/Compound Heterozygous 1 PMS2 1 NF1 1 MUTYH-Biallelic/Compound Heterozygous 1 PTEN 1 MSH3 1 FH 1 BRCA2 1 Total Melanoma w/o Breast Cancer PVs 21 Total Melanoma w/Breast Cancer PVs 10

Citation Format: Peter Beitsch, Chloe Wernecke, Kelly Bontempo, Brenna Bentley, Pat Whitworth, Rakesh Patel. Germline pathogenic variants in melanoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB163.