Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Dec 1;110(12):1380-1385.
doi: 10.1093/jnci/djy058.

A Nonsynonymous Variant in the GOLM1 Gene in Cutaneous Malignant Melanoma

Craig C Teerlink  1 , Chad Huff  2 , Jeff Stevens  1 , Yao Yu  2 , Sheri L Holmen  3   4 , Mark R Silvis  3 , Kirby Trombetti  3 , Hua Zhao  2 , Douglas Grossman  3   5 , James M Farnham  1 , Jingran Wen  6 , Julio C Facelli  7 , Alun Thomas  1 , Markus Babst  8   9 , Scott R Florell  5 , Laurence Meyer  5   10 , John J Zone  5 , Sancy Leachman  11 , Lisa A Cannon-Albright  1   3
Affiliations

A Nonsynonymous Variant in the GOLM1 Gene in Cutaneous Malignant Melanoma

Craig C Teerlink et al. J Natl Cancer Inst. .

Abstract

Background: Statistically significant linkage of melanoma to chromosome 9q21 was previously reported in a Danish pedigree resource and independently confirmed in Utah high-risk pedigrees, indicating strong evidence that this region contains a melanoma predisposition gene.

Methods: Whole-exome sequencing of pairs of related melanoma case subjects from two pedigrees with evidence of 9q21 linkage was performed to identify the responsible predisposition gene. Candidate variants were tested for association with melanoma in an independent set of 454 unrelated familial melanoma case subjects and 396 unrelated cancer-free control subjects from Utah, and 1534 melanoma case subjects and 1146 noncancer control subjects from Texas (MD Anderson) via a two-sided Fisher exact test.

Results: A rare nonsynonymous variant in Golgi Membrane Protein 1 (GOLM1), rs149739829, shared in two hypothesized predisposition carriers in one linked pedigree was observed. Segregation of this variant in additional affected relatives of the index carriers was confirmed. A statistically significant excess of carriers of the variant was observed among Utah case subjects and control subjects (odds ratio [OR] = 9.81, 95% confidence interval [CI] = 8.35 to 11.26, P < .001) and statistically significantly confirmed in Texas case subjects and control subjects (OR = 2.45, 95% CI = 1.65 to 3.25, P = .02).

Conclusion: These findings support GOLM1 as a candidate melanoma predisposition gene.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
High-risk cutaneous malignant melanoma (CMM) pedigree segregating a rare variant in GOLM1. Arrows indicate index predisposition haplotype carriers with whole-exome sequencing data, black fill indicates CMM diagnosis, + indicates carriage of the rare allele at rs149739829 confirmed by Sanger Sequencing, and (+) indicates inferred carriage.
See this image and copyright information in PMC

References

    1. Guy GP, Machlin SR, Ekwueme DU, Yabroff KR.. Prevalence and costs of skin cancer treatment in the US, 2002-2006 and 2007-2011. Am J Prev Med. 2015;482:183–187. - PMC - PubMed
    1. Howlader N, Noone AM, Krapcho M, et al., eds. SEER Cancer Statistics Review, 1975-2008. Bethesda, MD: National Cancer Institute; 2011.
    1. Teerlink CC, Albright FS, Lins L, Cannon-Albright LA.. A comprehensive survey of cancer risks in extended families. Genet Med. 2012;141:107–114. - PubMed
    1. Albright FS, Teerlink CC, Werner TL, Cannon-Albright LA.. Significant evidence for a heritable contribution to cancer predisposition: A review of cancer familiality by site. BMC Cancer. 2012;12:138. - PMC - PubMed
    1. Amundadottir LT, Thorvaldsson S, Gudbjartsson DF, et al. Cancer as a complex phenotype: Pattern of cancer distribution within and beyond the nuclear family. PLoS Med. 2004;13:e65. - PMC - PubMed

Publication types

MeSH terms