KIT gene mutations and copy number in melanoma subtypes

Carol Beadling, Erick Jacobson-Dunlop, F. Stephen Hodi, Claudia Le, Andrea Warrick, Janice Patterson, Ajia Town, Amy Harlow, Frank Cruz, Sharl Azar, Brian P. Rubin, Susan Muller, Rob West, Michael Heinrich, Christopher Corless

Research output: Contribution to journalArticle

405 Citations (Scopus)

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-ninemelanomas were screened formutations in KIT exons 11, 13, and 17. KIT copy number was assessed by quantitative PCR. As ubset 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% (1of 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 allmelanoma 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.

Original languageEnglish (US)
Pages (from-to)6821-6828
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number21
DOIs
StatePublished - Nov 1 2008

Fingerprint

Gene Dosage
Melanoma
Mutation
Extremities
Exons
Neoplasms
Skin
Mutation Rate
Research Design
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Beadling, C., Jacobson-Dunlop, E., Hodi, F. S., Le, C., Warrick, A., Patterson, J., ... Corless, C. (2008). KIT gene mutations and copy number in melanoma subtypes. Clinical Cancer Research, 14(21), 6821-6828. https://doi.org/10.1158/1078-0432.CCR-08-0575

KIT gene mutations and copy number in melanoma subtypes. / Beadling, Carol; Jacobson-Dunlop, Erick; Hodi, F. Stephen; Le, Claudia; Warrick, Andrea; Patterson, Janice; Town, Ajia; Harlow, Amy; Cruz, Frank; Azar, Sharl; Rubin, Brian P.; Muller, Susan; West, Rob; Heinrich, Michael; Corless, Christopher.

In: Clinical Cancer Research, Vol. 14, No. 21, 01.11.2008, p. 6821-6828.

Research output: Contribution to journalArticle

Beadling, C, Jacobson-Dunlop, E, Hodi, FS, Le, C, Warrick, A, Patterson, J, Town, A, Harlow, A, Cruz, F, Azar, S, Rubin, BP, Muller, S, West, R, Heinrich, M & Corless, C 2008, 'KIT gene mutations and copy number in melanoma subtypes', Clinical Cancer Research, vol. 14, no. 21, pp. 6821-6828. https://doi.org/10.1158/1078-0432.CCR-08-0575
Beadling C, Jacobson-Dunlop E, Hodi FS, Le C, Warrick A, Patterson J et al. KIT gene mutations and copy number in melanoma subtypes. Clinical Cancer Research. 2008 Nov 1;14(21):6821-6828. https://doi.org/10.1158/1078-0432.CCR-08-0575
Beadling, Carol ; Jacobson-Dunlop, Erick ; Hodi, F. Stephen ; Le, Claudia ; Warrick, Andrea ; Patterson, Janice ; Town, Ajia ; Harlow, Amy ; Cruz, Frank ; Azar, Sharl ; Rubin, Brian P. ; Muller, Susan ; West, Rob ; Heinrich, Michael ; Corless, Christopher. / KIT gene mutations and copy number in melanoma subtypes. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 21. pp. 6821-6828.
@article{941350b0c34947e5a9683dbee2f886de,
title = "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-ninemelanomas were screened formutations in KIT exons 11, 13, and 17. KIT copy number was assessed by quantitative PCR. As ubset 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{\%} (1of 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 allmelanoma 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.",
author = "Carol Beadling and Erick Jacobson-Dunlop and Hodi, {F. Stephen} and Claudia Le and Andrea Warrick and Janice Patterson and Ajia Town and Amy Harlow and Frank Cruz and Sharl Azar and Rubin, {Brian P.} and Susan Muller and Rob West and Michael Heinrich and Christopher Corless",
year = "2008",
month = "11",
day = "1",
doi = "10.1158/1078-0432.CCR-08-0575",
language = "English (US)",
volume = "14",
pages = "6821--6828",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "21",

}

TY - JOUR

T1 - KIT gene mutations and copy number in melanoma subtypes

AU - Beadling, Carol

AU - Jacobson-Dunlop, Erick

AU - Hodi, F. Stephen

AU - Le, Claudia

AU - Warrick, Andrea

AU - Patterson, Janice

AU - Town, Ajia

AU - Harlow, Amy

AU - Cruz, Frank

AU - Azar, Sharl

AU - Rubin, Brian P.

AU - Muller, Susan

AU - West, Rob

AU - Heinrich, Michael

AU - Corless, Christopher

PY - 2008/11/1

Y1 - 2008/11/1

N2 - 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-ninemelanomas were screened formutations in KIT exons 11, 13, and 17. KIT copy number was assessed by quantitative PCR. As ubset 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% (1of 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 allmelanoma 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.

AB - 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-ninemelanomas were screened formutations in KIT exons 11, 13, and 17. KIT copy number was assessed by quantitative PCR. As ubset 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% (1of 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 allmelanoma 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.

UR - http://www.scopus.com/inward/record.url?scp=58149260596&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149260596&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-08-0575

DO - 10.1158/1078-0432.CCR-08-0575

M3 - Article

C2 - 18980976

AN - SCOPUS:58149260596

VL - 14

SP - 6821

EP - 6828

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 21

ER -