Literature DB >> 21204718

Progressive genetic alterations of adenoid cystic carcinoma with high-grade transformation.

Raja R Seethala1, Kathleen Cieply, E Leon Barnes, Sanja Dacic.   

Abstract

CONTEXT: Although genome-wide imbalances have been characterized in conventional adenoid cystic carcinoma, other than p53 mutational status, the molecular profile of adenoid cystic carcinoma with high-grade transformation has not been explored.
OBJECTIVE: To evaluate progressive genetic alterations in adenoid cystic carcinoma with high-grade transformation using array comparative genomic hybridization.
DESIGN: Five adenoid cystic carcinomas with high-grade transformation (4 primary tumors and 1 paired metastasis) were selected and characterized at the DNA level by array comparative genomic hybridization on formalin-fixed paraffin-embedded tissue. Select alterations were validated by fluorescence in situ hybridization.
RESULTS: Chromosomal gains were mostly confined to the areas of high-grade transformation while losses were seen only in the conventional areas. Chromosomal regions with significant gains included 8q24, 17q11.2-q12, 17q23, and 15q11-13. Regions that showed the significant losses included 9q34, 4p16, 1p36.1, and 11q22. Fluorescence in situ hybridization analysis demonstrated increases in C-MYC (8q24.12-q24.13) and a low level increases in ERBB2 ( formerly HER2/neu ) (17q11.2-q12) in cases showing gains by array comparative genomic hybridization in these regions. However, no tumor showed HER2/ neu immunopositivity.
CONCLUSIONS: High-grade transformation in adenoid cystic carcinoma is a complex process that is reflected by several chromosomal alterations. Our findings implicate C-MYC amplification in this progression, although the role of HER2/neu is still unclear. Other candidate oncogenes, particularly on chromosome 17q23, warrant investigation in this rare tumor.

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Year:  2011        PMID: 21204718     DOI: 10.5858/2010-0048-OAR.1

Source DB:  PubMed          Journal:  Arch Pathol Lab Med        ISSN: 0003-9985            Impact factor:   5.534


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