High Resolution Analysis of Genome-Wide Copy Number Change in Neuroendocrine Carcinoma of the Breast
X Leng, R Shui, L Shen, KA Baggerly, X Liu, C Liu, A Sahin, SC Abraham, Y Wu. The University of Texas M. D. Anderson Cancer Center, Houston, TX; Cancer Hospital, Fudan University, Shanghai, China
Background: Neuroendocrine carcinoma (NEC) of the breast is an unusual subtype of breast carcinoma. Little is known about the genetic alterations involved in breast NEC.
Design: To gain a better understanding of the underlying mechanisms of breast NEC, genomic DNA were extracted from freshly collected tissues of six breast neuroendocrine carcinoma and three normal breast. The genomic DNA were labeled and hybridized to Affymetrix SNP array 6.0, which contains 946,000 probes for detection of changes in the gene copy numbers at genome-wide scale. The diagnoses of all six breast NEC cases were confirmed by immunohistochemical staining using neuroendocrine markers synaptophysin and/or chromogranin, with more than 50% of invasive tumor cells positive for one or both markers. The changes in the gene copy numbers were analyzed using Partek Genomic Suite software (Partek, Inc. St Louis, MO).
Results: The analyses showed that breast NEC samples displayed increased gene copy numbers in the two sets of chromosomal regions, one set contained genes invovled in neuronal or endocrinal functions (e.g. GRM8, EPHA7, prosaposin, PRIMA1, RAB27B, ACCN1, GPR337L1, ZHX2) and the other set contained genes involved in promoting cell cycle and tumorigenesis (e.g. FBXO11, DLG1, ZDHHC1, HINT1, FBXW11, DOCK5, MOS, PLAG1, FGF3, NCOA2). Accordingly, we found that chromosomal regions containing tumor suppressors (e.g. ELK3, ELAVL2, KITLG, WWOX) were deleted. Other deleted regions contained the genes involved in normal and neuronal development (e.g. CDH7, NFIB, DYNC2H1). We also detected changes in the copy numbers of a few genes with unknown function. In particular, SUSD1, a sushi domain containing protein 1, displayed increased copy numbers in all six breast NEC samples. The function of SUSD1 in breast NEC is not clear and needs further investigation.
Conclusions: A wide spectrum of genetic aberrations was identified in NEC of the breast. Additional studies will be needed to further explore the potential mechanisms in the development of breast NEC which involves the identified candidate genes from this study.
Category: Pan-genomic/Pan-proteomic Approaches to Diseases
Monday, March 22, 2010 1:00 PM
Poster Session II # 225, Monday Afternoon