Large-scale analysis of KIT aberrations in Chinese patients with melanoma

Yan Kong, Lu Si, Yanyan Zhu, Xiaowei Xu, Christopher Corless, Keith T. Flaherty, Li Li, Haifu Li, Xinan Sheng, Chuanliang Cui, Zhihong Chi, Siming Li, Mei Han, Lili Mao, Aiping Lu, Jun Guo

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149 Citations (Scopus)

Abstract

Purpose: KIT aberrations were described in acral and mucosal melanomas in largely Caucasian populations. Asian populations are more prone to develop acral and mucosal than cutaneous melanomas, and may harbor a high frequency of KIT aberrations. Experimental Design: Melanoma subtypes (n = 502) were analyzed histologically to determine melanoma subtype. Tissue samples were analyzed for mutations in exons 9, 11, 13, 17, and 18 of KIT gene in genomic DNA by PCR amplification and Sanger sequencing. The copy numbers of the KIT gene were analyzed by quantitative PCR, and protein expression levels of KIT (CD117) were determined by immunohistochemistry. Results: The most common melanoma subtypes were acral (38.4%) and mucosal (33.3%) melanomas in this population. The overall incidence of somatic mutations within the KIT gene was 10.8% (54/502), and all subtypes of melanoma contained KIT mutations. Increases in KIT gene copy numbers were correlated to CD117 overexpression. The genetic mutations of KIT were unrelated to the age, gender, stage, thickness, and ulceration of primary melanomas. Importantly, the overall survival of melanoma patients with KIT mutations (P = 0.001) or with KIT aberrations (mutation plus amplification, P = 0.0002) was significantly shorter than that of patients without such alterations. Conclusion: In China, the prevalent melanomas are acral and mucosal melanomas. KIT mutations are detected in all melanoma subtypes. Our study suggests that increases in KIT gene copy numbers, but not KIT mutations, may be correlated to CD117 overexpression. For the first time, our study suggests that genetic KIT aberration is an adverse prognostic factor for melanoma.

Original languageEnglish (US)
Pages (from-to)1684-1691
Number of pages8
JournalClinical Cancer Research
Volume17
Issue number7
DOIs
StatePublished - Apr 1 2011

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Melanoma
Mutation
Gene Dosage
Extremities
Population
Polymerase Chain Reaction
Experimental Melanomas
Genes
Exons
China
Research Design
Immunohistochemistry
Skin
Survival
DNA
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Large-scale analysis of KIT aberrations in Chinese patients with melanoma. / Kong, Yan; Si, Lu; Zhu, Yanyan; Xu, Xiaowei; Corless, Christopher; Flaherty, Keith T.; Li, Li; Li, Haifu; Sheng, Xinan; Cui, Chuanliang; Chi, Zhihong; Li, Siming; Han, Mei; Mao, Lili; Lu, Aiping; Guo, Jun.

In: Clinical Cancer Research, Vol. 17, No. 7, 01.04.2011, p. 1684-1691.

Research output: Contribution to journalArticle

Kong, Y, Si, L, Zhu, Y, Xu, X, Corless, C, Flaherty, KT, Li, L, Li, H, Sheng, X, Cui, C, Chi, Z, Li, S, Han, M, Mao, L, Lu, A & Guo, J 2011, 'Large-scale analysis of KIT aberrations in Chinese patients with melanoma', Clinical Cancer Research, vol. 17, no. 7, pp. 1684-1691. https://doi.org/10.1158/1078-0432.CCR-10-2346
Kong, Yan ; Si, Lu ; Zhu, Yanyan ; Xu, Xiaowei ; Corless, Christopher ; Flaherty, Keith T. ; Li, Li ; Li, Haifu ; Sheng, Xinan ; Cui, Chuanliang ; Chi, Zhihong ; Li, Siming ; Han, Mei ; Mao, Lili ; Lu, Aiping ; Guo, Jun. / Large-scale analysis of KIT aberrations in Chinese patients with melanoma. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 7. pp. 1684-1691.
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abstract = "Purpose: KIT aberrations were described in acral and mucosal melanomas in largely Caucasian populations. Asian populations are more prone to develop acral and mucosal than cutaneous melanomas, and may harbor a high frequency of KIT aberrations. Experimental Design: Melanoma subtypes (n = 502) were analyzed histologically to determine melanoma subtype. Tissue samples were analyzed for mutations in exons 9, 11, 13, 17, and 18 of KIT gene in genomic DNA by PCR amplification and Sanger sequencing. The copy numbers of the KIT gene were analyzed by quantitative PCR, and protein expression levels of KIT (CD117) were determined by immunohistochemistry. Results: The most common melanoma subtypes were acral (38.4{\%}) and mucosal (33.3{\%}) melanomas in this population. The overall incidence of somatic mutations within the KIT gene was 10.8{\%} (54/502), and all subtypes of melanoma contained KIT mutations. Increases in KIT gene copy numbers were correlated to CD117 overexpression. The genetic mutations of KIT were unrelated to the age, gender, stage, thickness, and ulceration of primary melanomas. Importantly, the overall survival of melanoma patients with KIT mutations (P = 0.001) or with KIT aberrations (mutation plus amplification, P = 0.0002) was significantly shorter than that of patients without such alterations. Conclusion: In China, the prevalent melanomas are acral and mucosal melanomas. KIT mutations are detected in all melanoma subtypes. Our study suggests that increases in KIT gene copy numbers, but not KIT mutations, may be correlated to CD117 overexpression. For the first time, our study suggests that genetic KIT aberration is an adverse prognostic factor for melanoma.",
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T1 - Large-scale analysis of KIT aberrations in Chinese patients with melanoma

AU - Kong, Yan

AU - Si, Lu

AU - Zhu, Yanyan

AU - Xu, Xiaowei

AU - Corless, Christopher

AU - Flaherty, Keith T.

AU - Li, Li

AU - Li, Haifu

AU - Sheng, Xinan

AU - Cui, Chuanliang

AU - Chi, Zhihong

AU - Li, Siming

AU - Han, Mei

AU - Mao, Lili

AU - Lu, Aiping

AU - Guo, Jun

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Purpose: KIT aberrations were described in acral and mucosal melanomas in largely Caucasian populations. Asian populations are more prone to develop acral and mucosal than cutaneous melanomas, and may harbor a high frequency of KIT aberrations. Experimental Design: Melanoma subtypes (n = 502) were analyzed histologically to determine melanoma subtype. Tissue samples were analyzed for mutations in exons 9, 11, 13, 17, and 18 of KIT gene in genomic DNA by PCR amplification and Sanger sequencing. The copy numbers of the KIT gene were analyzed by quantitative PCR, and protein expression levels of KIT (CD117) were determined by immunohistochemistry. Results: The most common melanoma subtypes were acral (38.4%) and mucosal (33.3%) melanomas in this population. The overall incidence of somatic mutations within the KIT gene was 10.8% (54/502), and all subtypes of melanoma contained KIT mutations. Increases in KIT gene copy numbers were correlated to CD117 overexpression. The genetic mutations of KIT were unrelated to the age, gender, stage, thickness, and ulceration of primary melanomas. Importantly, the overall survival of melanoma patients with KIT mutations (P = 0.001) or with KIT aberrations (mutation plus amplification, P = 0.0002) was significantly shorter than that of patients without such alterations. Conclusion: In China, the prevalent melanomas are acral and mucosal melanomas. KIT mutations are detected in all melanoma subtypes. Our study suggests that increases in KIT gene copy numbers, but not KIT mutations, may be correlated to CD117 overexpression. For the first time, our study suggests that genetic KIT aberration is an adverse prognostic factor for melanoma.

AB - Purpose: KIT aberrations were described in acral and mucosal melanomas in largely Caucasian populations. Asian populations are more prone to develop acral and mucosal than cutaneous melanomas, and may harbor a high frequency of KIT aberrations. Experimental Design: Melanoma subtypes (n = 502) were analyzed histologically to determine melanoma subtype. Tissue samples were analyzed for mutations in exons 9, 11, 13, 17, and 18 of KIT gene in genomic DNA by PCR amplification and Sanger sequencing. The copy numbers of the KIT gene were analyzed by quantitative PCR, and protein expression levels of KIT (CD117) were determined by immunohistochemistry. Results: The most common melanoma subtypes were acral (38.4%) and mucosal (33.3%) melanomas in this population. The overall incidence of somatic mutations within the KIT gene was 10.8% (54/502), and all subtypes of melanoma contained KIT mutations. Increases in KIT gene copy numbers were correlated to CD117 overexpression. The genetic mutations of KIT were unrelated to the age, gender, stage, thickness, and ulceration of primary melanomas. Importantly, the overall survival of melanoma patients with KIT mutations (P = 0.001) or with KIT aberrations (mutation plus amplification, P = 0.0002) was significantly shorter than that of patients without such alterations. Conclusion: In China, the prevalent melanomas are acral and mucosal melanomas. KIT mutations are detected in all melanoma subtypes. Our study suggests that increases in KIT gene copy numbers, but not KIT mutations, may be correlated to CD117 overexpression. For the first time, our study suggests that genetic KIT aberration is an adverse prognostic factor for melanoma.

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