Cancer Res Treat.  2018 Oct;50(4):1378-1387. 10.4143/crt.2017.535.

Genetic Alterations among Korean Melanoma Patients Showing Tumor Heterogeneity: A Comparison between Primary Tumors and Corresponding Metastatic Lesions

• Lee SH
• Kim JE
• Jang HS
• Park KH
• Oh BH
• Shin SJ
• Chung KY
• Roh MR
• Rha SY

• KMID: 2424809
• DOI: http://doi.org/10.4143/crt.2017.535

Abstract

PURPOSE
Melanoma is a highly heterogeneous neoplasm, composed of subpopulations of tumor cells with distinct molecular and biological phenotypes and genotypes. In this study, to determine the genetic heterogeneity between primary and metastatic melanoma in Korean melanoma patients, we evaluated several well-known genetic alterations of melanoma. In addition, to elucidate the clinical relevance of each genetic alteration and heterogeneity between primary and metastatic lesions, clinical features and patient outcome were collected.
MATERIALS AND METHODS
In addition to clinical data, BRAF, NRAS, GNAQ/11 mutation and KIT amplification data was acquired from an archived primary Korean melanoma cohort (KMC) of 188 patients. Among these patients, 43 patients were included for investigation of tumor heterogeneity between primary melanoma and its corresponding metastatic lesions.
RESULTS
Overall incidence of genetic aberrations of the primary melanomas in KMC was 17.6% of BRAF V600, 12.6% of NRAS mutation, and 28.6% of KIT amplification. GNAQ/11 mutation was seen in 66.6% of the uveal melanoma patients. Patients with BRAF mutation were associated with advanced stage and correlated to poor prognosis (p < 0.01). Among 43 patients, 55.8% showed heterogeneity between primary and metastatic lesion. The frequency of BRAF mutation and KIT amplification significantly increased in the metastatic lesions compared to primary melanomas. GNAQ/11 mutation showed 100% homogeneity in uveal melanoma patients.
CONCLUSION
Our data demonstrated heterogeneity between primary melanomas and corresponding metastatic lesions for BRAF, NRAS mutation and KIT amplification. However, GNAQ/11 mutation was genetically homogeneous between primary and metastatic melanoma lesions in uveal melanoma.

Keyword

Melanoma; Heterogeneity; BRAF; KIT; NRAS

MeSH Terms

Cohort Studies
Genetic Heterogeneity
Genotype
Humans
Incidence
Melanoma*
Phenotype
Population Characteristics*
Prognosis

Figure

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  Fig. 1. Study overview. LN, lymph node; CSD, chronic sun-induced damage; UP, unknown primary; PCR, polymerase chain reaction.

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  Fig. 2. Overall survivals of melanoma patients in relation to genetic aberrations. (A) Overall survival in relation to BRAF mutation. (B) Overall survival in relation to NRAS mutation. (C) Overall survival in relation to KIT amplification. (D) Overall survival in relation to BRAF mutation in stage 1 and 2 patients. (E) Overall survival in relation to BRAF mutation in stage 3 and 4 patients.

• 

  Fig. 3. Comparison of survival in melanoma patients according to genetic heterogeneity. (A) 5-Year survival according to genetic concordancy. (B) 5-Year survival according to discordance in metastatic sites. (C) 5-Year survival according to synchronous and metachronous discordance. N, lymph node metastasis; M, distant metastasis; Syn, synchronous; Meta, metachronous.

Reference

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