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

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 b...

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Bibliographic Details
Published in:	Marshall journal of medicine Vol. 3; no. 2; pp. 65 - 73
Main Authors:	Smith Jr, Brent J., Hintzsche, Jennifer D., Amato, Carol M., Tan, Aik-Choon, Wells, Keith R., Applegate, Allison J., Gonzalez, Rita T., Barr, Jodie R., Robinson, William A.
Format:	Journal Article
Language:	English
Published:	Marshall University 01-04-2017
Subjects:	G691S germline variant melanoma RETp whole exome sequencing
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Summary:	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.
ISSN:	2379-9536 2379-9536
DOI:	10.18590/mjm.2017.vol3.iss2.10