Systematic Analysis of Whole Exome Sequencing Determines RET G691S Polymorphism as Germline Variant in Melanoma

Authors

Brent J. Smith Jr, Marshall University Joan C. Edwards School of MedicineFollow
Jennifer D. Hintzsche, University of Colorado Cancer CenterFollow
Carol M. Amato, University of Colorado Cancer CenterFollow
Aik-Choon Tan, University of Colorado Cancer CenterFollow
Keith R. Wells, University of Colorado Cancer CenterFollow
Allison J. Applegate, University of Colorado Cancer CenterFollow
Rita T. Gonzalez, University of Colorado Cancer CenterFollow
Jodie R. Barr, University of Colorado Cancer CenterFollow
William A. Robinson, University of Colorado Cancer CenterFollow

Author Credentials

Brent J. Smith, Jr., MSIII, Jennifer D. Hintzsche, PhD, Carol M. Amato, MS, Aik-Choon Tan, PhD, Keith R. Wells, MD, Allison J. Applegate, BS, Rita T. Gonzalez, MD, Jodie R. Barr, DO, William A. Robinson, MD, PhD

Keywords

RETp, G691S, melanoma, whole exome sequencing, germline variant

Disciplines

Dermatology | Genomics | Neoplasms | Oncology

Abstract

Abstract

The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by glial cell derived neutrotrophic factor (GDNF). Previous studies have found that a single nucleotide polymorphism (SNP), RETp (G691S), in the juxtamembrane domain enhances the signaling pathway and promotes tumor growth by GDNF in pancreatic and thyroid cancer in addition to melanoma. It is uncertain however whether this SNP is a germline variant or somatic mutation. A prior study reported that the RETp variant was a germline SNP in desmoplastic and non-desmoplastic melanomas. In the present study, we examined both melanoma tissue samples and matching peripheral blood DNA to determine if RETp was 1) a germline or somatic variant, 2) more frequent in certain melanoma subtypes, and 3) frequency in brain metastasis. We examined the peripheral blood of 197 melanoma patients whom had at least one matched tumor, and 42 patients with brain metastasis. RETp was present as a germline SNP in 33% of patients. There were no significant differences in RETp frequency among the different melanoma subtypes, and RETp was not correlated with brain metastasis.

Recommended Citation

Smith BJ, Hintzsche JD, Amato CM, et al. Systematic Analysis of Whole Exome Sequencing Determines RET G691S Polymorphism as Germline Variant in Melanoma. Marshall J Med. 2017; 3(2): 65 DOI: