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 C.
AU - Corless, Christopher L.
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.
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U2 - 10.1158/1078-0432.CCR-08-0575
DO - 10.1158/1078-0432.CCR-08-0575
M3 - Article
C2 - 18980976
AN - SCOPUS:58149260596
SN - 1078-0432
VL - 14
SP - 6821
EP - 6828
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 21
ER -