Development of a gene signature to predict positive or negative sentinel nodes as a prognostic marker in melanoma
In recent years, sentinel lymph node (SLN) biopsy has been adopted as a less invasive technique to assess the prognostic outcome of melanoma, whereby draining the key lymph nodes for presence of a tumor decreases unnecessary lymph node dissections and reduces the risk of developing lymphedema. However, this technique only has therapeutic value in patients with SLN-positive tumor nodes, which only represents about half of the population diagnosed with melanoma. In a pilot study, we assessed the predictive efficacy of using a commercialized multi-biomarker next-generation sequencing (NGS) assay (Illumina® Comprehensive Cancer Panel) containing selected genes which have been shown to have a prognostic impact in melanoma progression, to determine whether these can identify primary tumors which do not require SLN biopsy. We used laser capture microdissection to capture pathologist-identified areas of tumor from four groups of samples 1) skin lesions from SLN-positive patients, 2) skin lesions from SLN-negative patients, 3) node samples from SLN-positive patients and node samples from SLN-negative patients; some cases of skin lesions and nodes were matched for the same patient. Sequencing identified 14 genes containing variants in >70% of the positive node samples, which were absent in samples with negative nodes. This included EGFR, PDGFR, ATM, PIK3CA, TP53 and ERBB4. Of note, variants in ERBB4 is of interest as it has been shown in the past to be a potential molecular target in the treatment of melanoma. We are currently validating these preliminary findings in a larger cohort of patients (n=31) and will report on the NGS findings of this study and the efficacy of using genetic biomarkers in skin biopsy samples as a potential prognostic marker for early stage melanoma patients who may not require SLN biopsy.
Audrey J. Majeske, Timothy J. Geddes, Richard Keidan, George D. Wilson. Development of a gene signature to predict positive or negative sentinel nodes as a prognostic marker in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2412.