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 C, Corless Christopher L
Oregon Cancer Institute, Oregon Health & Science University, Portland, Oregon 97239, USA.
Clin Cancer Res. 2008 Nov 1;14(21):6821-8. doi: 10.1158/1078-0432.CCR-08-0575.
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.
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.
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.
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.
我们最近在一名对伊马替尼治疗反应良好的肛管黑色素瘤患者中发现了KIT外显子11突变。为了确定KIT突变在黑色素瘤各亚型中的频率，我们对一大系列肿瘤进行了调查。
对189例黑色素瘤进行KIT外显子11、13和17突变的筛查。通过定量PCR评估KIT拷贝数。对一部分病例评估BRAF和NRAS突变情况。采用免疫组织化学方法评估KIT（CD117）表达。
在肢端黑色素瘤中，23%（13例中的3例）检测到KIT突变；黏膜黑色素瘤中为15.6%（45例中的7例）；结膜黑色素瘤中为7.7%（13例中的1例）；皮肤黑色素瘤中为1.7%（58例中的1例）；脉络膜黑色素瘤中未检测到（60例中的0例）。几乎所有KIT突变都是预测对伊马替尼敏感的类型。与NRAS突变（肢端肿瘤中的11.1%和黏膜肿瘤中的24.3%）或BRAF突变（黏膜肿瘤中未出现）无重叠。在肢端黑色素瘤的27.3%（11例中的3例）和黏膜黑色素瘤的26.3%（38例中的10例）中检测到KIT拷贝数增加，但在皮肤（6.7%；45例中的3例）、结膜（7.1%；14例中的1例）和脉络膜黑色素瘤（28例中的0例）中较少见。在代表所有黑色素瘤类型的105例肿瘤中，39%表达CD117，其与KIT突变状态或KIT拷贝数均无相关性。
我们的研究结果证实，KIT突变在肢端和黏膜黑色素瘤中最常见，但不一定与KIT拷贝数或CD117表达相关。筛查KIT突变可能为黑色素瘤患者开辟新的治疗选择。
