Identification of c-kit gene mutations in primary adenoid cystic carcinoma of the salivary gland

Lizette Vila, Hongyan Liu, Samer Z. Al-Quran, Dominique P. Coco, Hui Jia Dong, Chen Liu

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

The CD117 (KIT) protein is overexpressed in many human neoplasms including adenoid cystic carcinoma of salivary glands. To evaluate the function of c-kit-activating mutations in adenoid cystic carcinoma of the salivary gland, we studied 14 cases (13 primary, 1 cervical lymph node metastasis) from our institution. KIT protein expression was evaluated by immunohistochemistry using formalin-fixed paraffin-embedded tissue. Mutational analyses of c-kit extracellular (exon 9), juxtamembrane (exon 11) and tyrosine kinase domains (exons 13 and 17) were performed by polymerase chain reaction, clonal selection and DNA sequencing. All 14 cases demonstrated strong KIT expression by immunohistochemistry. Molecular analysis was successful in 8 of 14 cases, and c-kit missense point mutations were detected in seven of eight cases (88%) including seven in exon 11, two in exon 9, two in exon 13 and two in exon 17. Eight silent point mutations were detected in five cases. Two cases contained missense mutations in more than one exon. Different mutations were found in the primary tumor and the cervical lymph node metastasis of one patient. Point mutations in domains similar to those described in gastrointestinal stromal tumors were detected, including Pro551Leu and Lys558Glu (5′ end of exon 11), Leu576Phe (3′ end of exon 11), Val643Ala (exon 13) and Asn822Ser (exon 17). Additional novel point mutations in exons 9, 11, 13 and 17 were also identified. This study is the first to report c-kit gene mutations in primary adenoid cystic carcinoma of the salivary gland. Identification of such potential gain-of-function mutations in exon 11, and less frequently in exons 9, 13 and 17, suggests that KIT may be involved in the pathogenesis of adenoid cystic carcinoma of salivary glands. Our study raises a prospect of correlation of c-kit mutation and a potential treatment of adenoid cystic carcinoma with tyrosine kinase inhibitor (imatinib).

Original languageEnglish (US)
Pages (from-to)1296-1302
Number of pages7
JournalModern Pathology
Volume22
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Keywords

  • Adenoid cystic carcinoma
  • C-kit gene mutations
  • KIT protein
  • Salivary gland

Fingerprint

Dive into the research topics of 'Identification of c-kit gene mutations in primary adenoid cystic carcinoma of the salivary gland'. Together they form a unique fingerprint.

Cite this