KIT gene mutations and copy number in melanoma subtypes
- PMID: 18980976
- DOI: 10.1158/1078-0432.CCR-08-0575
KIT gene mutations and copy number in melanoma subtypes
Abstract
Purpose: We recently identified a KIT exon 11 mutation in an anorectal melanoma of a patient who had an excellent response to treatment with imatinib. To determine the frequency of KIT mutations across melanoma subtypes, we surveyed a large series of tumors.
Experimental design: One hundred eighty-nine melanomas were screened for mutations in KIT exons 11, 13, and 17. KIT copy number was assessed by quantitative PCR. A subset of cases was evaluated for BRAF and NRAS mutations. Immunohistochemistry was done to assess KIT (CD117) expression.
Results: KIT mutations were detected in 23% (3 of 13) of acral melanomas, 15.6% (7 of 45) of mucosal melanomas, 7.7% (1 of 13) of conjunctival melanomas, 1.7% (1 of 58) of cutaneous melanomas, and 0% (0 of 60) of choroidal melanomas. Almost all the KIT mutations were of the type predicted to be imatinib sensitive. There was no overlap with NRAS mutations (11.1% of acral and 24.3% of mucosal tumors) or with BRAF mutations (absent in mucosal tumors). Increased KIT copy number was detected in 27.3% (3 of 11) of acral and 26.3% (10 of 38) of mucosal melanomas, but was less common among cutaneous (6.7%; 3 of 45), conjunctival (7.1%; 1 of 14), and choroidal melanomas (0 of 28). CD117 expression, present in 39% of 105 tumors representing all melanoma types, did not correlate with either KIT mutation status or KIT copy number.
Conclusions: Our findings confirm that KIT mutations are most common in acral and mucosal melanomas but do not necessarily correlate with KIT copy number or CD117 expression. Screening for KIT mutations may open up new treatment options for melanoma patients.
Similar articles
-
KIT amplification and gene mutations in acral/mucosal melanoma in Korea.APMIS. 2011 Jun;119(6):330-5. doi: 10.1111/j.1600-0463.2011.02737.x. Epub 2011 Mar 24. APMIS. 2011. PMID: 21569090
-
GAB2 amplifications refine molecular classification of melanoma.Clin Cancer Res. 2009 Jul 1;15(13):4288-91. doi: 10.1158/1078-0432.CCR-09-0280. Epub 2009 Jun 9. Clin Cancer Res. 2009. PMID: 19509136 Free PMC article.
-
[ Spectrum of oncogene mutations is different in melanoma subtypes].Mol Biol (Mosk). 2015 Nov-Dec;49(6):1022-9. doi: 10.7868/S0026898415060166. Mol Biol (Mosk). 2015. PMID: 26710785 Russian.
-
BRAF and NRAS mutations are uncommon in melanomas arising in diverse internal organs.J Clin Pathol. 2005 Jun;58(6):640-4. doi: 10.1136/jcp.2004.022509. J Clin Pathol. 2005. PMID: 15917418 Free PMC article. Review.
-
Molecular pathogenesis of malignant melanoma: a different perspective from the studies of melanocytic nevus and acral melanoma.Pigment Cell Melanoma Res. 2010 Feb;23(1):64-71. doi: 10.1111/j.1755-148X.2009.00645.x. Epub 2009 Sep 25. Pigment Cell Melanoma Res. 2010. PMID: 19788535 Review.
Cited by
-
Mutation profile of primary subungual melanomas in Caucasians.Oncotarget. 2020 Jun 23;11(25):2404-2413. doi: 10.18632/oncotarget.27642. eCollection 2020 Jun 23. Oncotarget. 2020. PMID: 32637031 Free PMC article.
-
Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management.Int J Mol Sci. 2023 Nov 1;24(21):15881. doi: 10.3390/ijms242115881. Int J Mol Sci. 2023. PMID: 37958863 Free PMC article. Review.
-
Optimal management of metastatic melanoma: current strategies and future directions.Am J Clin Dermatol. 2013 Jun;14(3):179-94. doi: 10.1007/s40257-013-0025-9. Am J Clin Dermatol. 2013. PMID: 23677693 Free PMC article. Review.
-
Metabolic response by FDG-PET to imatinib correlates with exon 11 KIT mutation and predicts outcome in patients with mucosal melanoma.Cancer Imaging. 2014 Nov 12;14(1):30. doi: 10.1186/s40644-014-0030-0. Cancer Imaging. 2014. PMID: 25609545 Free PMC article. Clinical Trial.
-
The Relationship between KIT Copy Number Variation, Protein Expression, and Angiogenesis in Sporadic Breast Cancer.Rep Biochem Mol Biol. 2020 Apr;9(1):40-49. doi: 10.29252/rbmb.9.1.40. Rep Biochem Mol Biol. 2020. PMID: 32821750 Free PMC article.
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous