KIT mutations in Russian patients with mucosal melanoma

A single institution series of 48 mucosal melanomas (MMs) has been analyzed for the presence of KIT mutations using high-resolution melting and sequencing of abnormally melted DNA fragments. The analysis of exons 9, 11, 13, and 17 has revealed eight of 48 (17%) nonsynonymous alterations, including zero of seven head and neck, six of 24 anorectal, one of 15 genitourinary, one of one gastric, and zero of one mediastinal MMs. Seven of these mutations were potentially associated with the tumor sensitivity to KIT tyrosine kinase inhibitors. One tumor harbored somatically acquired silent nucleotide substitution c.1383A>G (T461T). This study adds to the evidence that a substantial portion of MMs carry a therapeutically relevant mutation in the KIT oncogene.

[1]  Y. Shinomura,et al.  Anorectal melanoma with a KIT-activating mutation, which is a target for tyrosine kinase inhibitor , 2011, International Journal of Clinical Oncology.

[2]  K. Flaherty,et al.  Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  C. Antonescu,et al.  KIT as a therapeutic target in metastatic melanoma. , 2011, JAMA.

[4]  S. Davis,et al.  Exome sequencing identifies GRIN2A as frequently mutated in melanoma , 2011, Nature Genetics.

[5]  K. Flaherty,et al.  Large-Scale Analysis of KIT Aberrations in Chinese Patients with Melanoma , 2011, Clinical Cancer Research.

[6]  P. Devilee,et al.  Non-founder BRCA1 mutations in Russian breast cancer patients. , 2010, Cancer letters.

[7]  S. Duensing,et al.  Targeted therapies of gastrointestinal stromal tumors (GIST)--the next frontiers. , 2010, Biochemical pharmacology.

[8]  S. Woodman,et al.  Targeting KIT in melanoma: a paradigm of molecular medicine and targeted therapeutics. , 2010, Biochemical pharmacology.

[9]  P. Ott,et al.  Mucosal melanomas: a case-based review of the literature. , 2010, The oncologist.

[10]  J. Coebergh,et al.  Epidemiology of Extracutaneous Melanoma in the Netherlands , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[11]  A. Dobrovic,et al.  Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT , 2010, British Journal of Cancer.

[12]  S. Woodman,et al.  Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acral-lentiginous/mucosal type , 2009, Modern Pathology.

[13]  Y. Kanai,et al.  Esophageal melanomas harbor frequent NRAS mutations unlike melanomas of other mucosal sites , 2009, Virchows Archiv.

[14]  T. Saida,et al.  Pathological activation of KIT in metastatic tumors of acral and mucosal melanomas , 2009, International journal of cancer.

[15]  R. Gutzmer,et al.  Analysis of c-KIT expression and KIT gene mutation in human mucosal melanomas , 2008, British Journal of Cancer.

[16]  Susan Muller,et al.  KIT Gene Mutations and Copy Number in Melanoma Subtypes , 2008, Clinical Cancer Research.

[17]  H. Nagatsuka,et al.  C-kit protein expression correlated with activating mutations in KIT gene in oral mucosal melanoma , 2008, Virchows Archiv.

[18]  Narasimhan P. Agaram,et al.  L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition , 2007, International journal of cancer.

[19]  D. Pinkel,et al.  Somatic activation of KIT in distinct subtypes of melanoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  L. Layfield,et al.  BRAF and c-kit gene copy number in mutation-positive malignant melanoma. , 2006, Human pathology.

[21]  J. Fridlyand,et al.  Distinct sets of genetic alterations in melanoma. , 2005, The New England journal of medicine.

[22]  Adrian A Canutescu,et al.  Analysis of KIT Mutations in Sporadic and Familial Gastrointestinal Stromal Tumors: Therapeutic Implications through Protein Modeling , 2005, Clinical Cancer Research.

[23]  Ahmedin Jemal,et al.  Incidence of noncutaneous melanomas in the U.S. , 2005, Cancer.