Dataset Information

Frequent Occurrence of NRAS and BRAF Mutations in Human Acral Naevi.

ABSTRACT: Acral naevi are benign melanocytic tumors occurring at acral sites. Occasionally they can progress to become malignant tumors (melanomas). The genetics of acral naevi have not been assessed in larger studies. In our study, a large cohort of 130 acral naevi was screened for gene mutations known to be important in other naevi and melanoma subtypes by targeted next-generation sequencing. Mutation status was correlated with clinicopathological parameters. Frequent mutations in genes activating the MAP kinase pathway were identified, including n = 87 (67%) BRAF, n = 24 (18%) NRAS, and one (1%) MAP2K1 mutations. BRAF mutations were almost exclusively V600E (n = 86, 99%) and primarily found in junctional and compound naevi. NRAS mutations were either Q61K or Q61R and frequently identified in dermal naevi. Recurrent non-V600E BRAF, KIT, NF1, and TERT promoter mutations, present in acral melanoma, were not identified. Our study identifies BRAF and NRAS mutations as the primary pathogenic event in acral naevi, however, distributed differently to those in non-acral naevi. The mutational profile of acral naevi is distinct from acral melanoma, which may be of diagnostic value in distinguishing these entities.

SUBMITTER: Jansen P

PROVIDER: S-EPMC6520878 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Frequent Occurrence of <i>NRAS</i> and <i>BRAF</i> Mutations in Human Acral Naevi.

Jansen Philipp P Cosgarea Ioana I Murali Rajmohan R Möller Inga I Sucker Antje A Franklin Cindy C Paschen Annette A Zaremba Anne A Brinker Titus J TJ Stoffels Ingo I Schadendorf Dirk D Klode Joachim J Hadaschik Eva E Griewank Klaus G KG

Cancers 20190416 4

Acral naevi are benign melanocytic tumors occurring at acral sites. Occasionally they can progress to become malignant tumors (melanomas). The genetics of acral naevi have not been assessed in larger studies. In our study, a large cohort of 130 acral naevi was screened for gene mutations known to be important in other naevi and melanoma subtypes by targeted next-generation sequencing. Mutation status was correlated with clinicopathological parameters. Frequent mutations in genes activating the M ...[more]

PMID: 30995742

Similar Datasets

Project description:To determine the expression of ?-catenin, lymphoid enhancer-binding protein-1 (LEF-1), and heparanase-1 (HPA-1) and to evaluate these proteins' potential prognostic values in malignant acral melanoma without mutations in BRAF exons 11 and 15 and NRAS exons 1 and 2, specimens from 90 patients with wild-type BRAF and NRAS were assessed and analyzed by immunohistochemistry and western blotting. The positive expression of ?-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was observed in 36 (72%), 31 (62%), and 32 (64%) of the detected acral melanomas, respectively. The expression of ?-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was not correlated with gender, age, or diseased body parts (p>0.05), but was significantly positively correlated with the tumor node metastasis (TNM) stage and metastasis (correlation=0.406 and 0.716, 0.397 and 0.582, 0.353 and 0.579; p=0.040 and 0.0001, 0.0040 and 0.0001, 0.0120 and 0.0001, respectively). We also observed that the increased expression of ?-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was significantly correlated with decreased survival and poor prognosis (p=0.001, 0.010, and 0.023, respectively). A multifactorial analysis using Cox's regression model revealed that ?-catenin, lymphoid enhancer-binding protein-1, heparanase-1, and the TNM stage were all independent factors in malignant melanoma (risk ratios were 7.294, 5.550, 5.622, and 4.794; p-values were 0.007, 0.018, 0.018, and 0.029, respectively). This study may provide the basis for the use of ?-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 as novel targets in the treatment of malignant invasion and metastasis in acral melanoma cancer. The expression of ?-catenin, LEF-1, and HPA-1 was assessed and compared in malignant melanoma with that of peritumoral tissue and benign nevus in the patients with negative mutations in BRAF exons 11 and 15 and NRAS exons 1 and 2. The study may provide the basis for ?-catenin, LEF-1, and HPA-1 as new targets in the treatment of malignant invasion and metastasis in melanoma cancer.

Dataset Information

Frequent Occurrence of NRAS and BRAF Mutations in Human Acral Naevi.

Publications

Frequent Occurrence of <i>NRAS</i> and <i>BRAF</i> Mutations in Human Acral Naevi.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets