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Updated: Sep 21, 2025
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
BRAF, NRAS, KIT, TERT, GNAQ/GNA11 Mutation Profile and Histomorphological Analysis of Anorectal Melanomas: A
Orhun Cig Taskin1, Sule Ozturk Sari, Ismail Yilmaz
1Department of Pathology, Istanbul University, Istanbul Faculty of Medicine, ISTANBUL, TURKEY.
Objective:
Primary anorectal melanomas (AMs) are uncommon neoplasms with aggressive behavior. Molecular profile and clinicopathologic features of AMs are still not well established. In this study, we aimed to investigate BRAF, NRAS, KIT, TERT, and GNAQ/GNA11 mutation status and clinicopathologic features of AMs.
Material And Method:
All diagnostic slides of 15 AMs were reviewed. Histopathological and follow-up information were documented. Mutations in exon 15 of the BRAF gene; exons 2 and 3 of the NRAS gene; exons 9, 11, 13, 17, and 18 of the KIT gene; and exons 4 and 5 of the GNAQ/GNA11 genes and mutations in the promoter region of the TERT gene (chr.5, 1,295,228C > T and 1,295,250C > T) were analyzed.
Results:
BRAF(V600E) and KIT(V555I and K642E) mutations were observed in one (7%) and two cases (14%), respectively. NRAS, TERT and GNAQ/GNA11 mutations were not detected. The mean age was 65. Patients presented with rectal mass, rectal bleeding, pain, and weight loss. 73% of the lesions were macroscopically polypoid. The most common tumor cell type was epithelioid. Mean tumor thickness was 10.4 mm. One third of the cases lacked pigmentation. In situ melanoma was present in one third of the cases. Among 14 patients with follow-up data, 12 succumbed to disease. The mean overall survival was 36 months.
Conclusion:
AMs are uncommon tumors with dismal survival, usually occurring in the elderly in various gross and microscopic appearances. In terms of molecular profile, BRAF and KIT mutations are rarely detected. Profiling of larger cohorts is required to elucidate the pathogenesis and to identify potential molecular indicators that may contribute to the development of individualized targeted therapies.
Insights
Primary anorectal melanomas (AMs) are rare, aggressive cancers. This study found BRAF and KIT mutations in a small percentage of AMs, with poor survival rates overall. Further research is needed for targeted therapies.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Pathology
Background:
- Primary anorectal melanomas (AMs) are rare and aggressive neoplasms.
- The molecular profile and clinicopathologic features of AMs are not well-established.
Purpose of the Study:
- To investigate the mutation status of BRAF, NRAS, KIT, TERT, and GNAQ/GNA11 genes in AMs.
- To analyze the clinicopathologic features of AMs.
Main Methods:
- Review of diagnostic slides from 15 AMs.
- Histopathological analysis and documentation of follow-up information.
- Mutation analysis for BRAF, NRAS, KIT, GNAQ/GNA11, and TERT genes.
Main Results:
- BRAF(V600E) and KIT mutations were found in 7% and 14% of cases, respectively.
- NRAS, TERT, and GNAQ/GNA11 mutations were not detected.
- The study observed poor survival, with a mean overall survival of 36 months.
Conclusions:
- AMs are uncommon tumors with dismal survival, often presenting in the elderly.
- BRAF and KIT mutations are rarely detected in AMs.
- Larger cohort profiling is necessary to understand AM pathogenesis and identify therapeutic targets.
