Nonoverlapping Clinical and Mutational Patterns in Melanomas from the Female Genital Tract and Atypical Genital Nevi

Overview

Journal J Invest Dermatol

Publisher Elsevier

Specialty Dermatology

Date 2016 May 26

PMID 27220476

Citations 6

Authors

Oriol Yelamos

Emily A Merkel

Lauren Meldi Sholl

Bin Zhang

Sapna M Amin

Christina Y Lee

Gerta E Guitart

Jingyi Yang

Alexander T Wenzel

Christopher G Bunick

Pedram Yazdan

Jaehyuk Choi

Pedram Gerami

Affiliations

Soon will be listed here.

Abstract

Genital melanomas (GM) are the second most common cancer of the female external genitalia and may be confused with atypical genital nevi (AGN), which exhibit atypical histological features but have benign behavior. In this study, we compared the clinical, histological, and molecular features of 19 GM and 25 AGN. We described chromosomal copy number aberrations and the mutational status of 50 oncogenes and tumor suppressor genes in both groups. Our study showed that a pigmented lesion occurring in mucosal tissue, particularly in postmenopausal women, was more likely to be a melanoma than a nevus. GM had high levels of chromosomal instability, with many copy number aberrations. Furthermore, we found a completely nonoverlapping pattern of oncogenic mutations when comparing GM and AGN. In GM, we report somatic mutations in KIT and TP53. Conversely, AGN had frequent BRAF V600E mutations, which were not seen in any of the GM. Our results show that GM and AGN have distinct clinical and molecular changes and that GM have a different mutational pattern compared with AGN.

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References

Forbes S, Beare D, Gunasekaran P, Leung K, Bindal N, Boutselakis H . COSMIC: exploring the world's knowledge of somatic mutations in human cancer. Nucleic Acids Res. 2014; 43(Database issue):D805-11. PMC: 4383913. DOI: 10.1093/nar/gku1075. View

Brenn T . Atypical genital nevus. Arch Pathol Lab Med. 2011; 135(3):317-20. DOI: 10.5858/2009-0382-RA.1. View

Tseng D, Kim J, Warrick A, Nelson D, Pukay M, Beadling C . Oncogenic mutations in melanomas and benign melanocytic nevi of the female genital tract. J Am Acad Dermatol. 2014; 71(2):229-36. PMC: 4450888. DOI: 10.1016/j.jaad.2014.03.033. View

Khan M, Khalil A, Rashid H . Evaluation of the p53 Arg72Pro polymorphism and its association with cancer risk: a HuGE review and meta-analysis. Genet Res (Camb). 2015; 97:e7. PMC: 6863642. DOI: 10.1017/S0016672315000075. View

Olivier M, Hollstein M, Hainaut P . TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol. 2010; 2(1):a001008. PMC: 2827900. DOI: 10.1101/cshperspect.a001008. View

Curtin J, Fridlyand J, Kageshita T, Patel H, Busam K, Kutzner H . Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005; 353(20):2135-47. DOI: 10.1056/NEJMoa050092. View

. Genomic Classification of Cutaneous Melanoma. Cell. 2015; 161(7):1681-96. PMC: 4580370. DOI: 10.1016/j.cell.2015.05.044. View

Sherry S, Ward M, Kholodov M, Baker J, Phan L, Smigielski E . dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2000; 29(1):308-11. PMC: 29783. DOI: 10.1093/nar/29.1.308. View

Cerami E, Gross B, Demir E, Rodchenkov I, Babur O, Anwar N . Pathway Commons, a web resource for biological pathway data. Nucleic Acids Res. 2010; 39(Database issue):D685-90. PMC: 3013659. DOI: 10.1093/nar/gkq1039. View

10.

Ewing B, Green P . Base-calling of automated sequencer traces using phred. II. Error probabilities. Genome Res. 1998; 8(3):186-94. View

11.

Shain A, Yeh I, Kovalyshyn I, Sriharan A, Talevich E, Gagnon A . The Genetic Evolution of Melanoma from Precursor Lesions. N Engl J Med. 2015; 373(20):1926-36. DOI: 10.1056/NEJMoa1502583. View

12.

Petitjean A, Achatz M, Borresen-Dale A, Hainaut P, Olivier M . TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene. 2007; 26(15):2157-65. DOI: 10.1038/sj.onc.1210302. View

13.

Curtin J, Busam K, Pinkel D, Bastian B . Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006; 24(26):4340-6. DOI: 10.1200/JCO.2006.06.2984. View

14.

Choi J, Goh G, Walradt T, Hong B, Bunick C, Chen K . Genomic landscape of cutaneous T cell lymphoma. Nat Genet. 2015; 47(9):1011-9. PMC: 4552614. DOI: 10.1038/ng.3356. View

15.

Krauthammer M, Kong Y, Ha B, Evans P, Bacchiocchi A, McCusker J . Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet. 2012; 44(9):1006-14. PMC: 3432702. DOI: 10.1038/ng.2359. View

16.

Tcheung W, Selim M, Herndon 2nd J, Abernethy A, Nelson K . Clinicopathologic study of 85 cases of melanoma of the female genitalia. J Am Acad Dermatol. 2012; 67(4):598-605. DOI: 10.1016/j.jaad.2011.11.921. View

17.

Tacastacas J, Bray J, Cohen Y, Arbesman J, Kim J, Koon H . Update on primary mucosal melanoma. J Am Acad Dermatol. 2014; 71(2):366-75. DOI: 10.1016/j.jaad.2014.03.031. View

18.

van Engen-van Grunsven A, Kusters-Vandevelde H, de Hullu J, van Duijn L, Rijntjes J, Bovee J . NRAS mutations are more prevalent than KIT mutations in melanoma of the female urogenital tract--a study of 24 cases from the Netherlands. Gynecol Oncol. 2014; 134(1):10-4. DOI: 10.1016/j.ygyno.2014.04.056. View

19.

EDWARDS R, Ward M, Wu H, Medina C, Brose M, Volpe P . Absence of BRAF mutations in UV-protected mucosal melanomas. J Med Genet. 2004; 41(4):270-2. PMC: 1735752. DOI: 10.1136/jmg.2003.016667. View

20.

Bennett D . How to make a melanoma: what do we know of the primary clonal events?. Pigment Cell Melanoma Res. 2008; 21(1):27-38. DOI: 10.1111/j.1755-148X.2007.00433.x. View