Clinical Implications of Gene Dosage and Gene Expression Patterns in Diploid Breast Carcinoma

Abstract

Purpose: Deregulation of key cellular pathways is fundamental for the survival and expansion of neoplastic cells. In cancer, regulation of gene transcription can be mediated in a variety of ways. The purpose of this study was to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels, and to associate these genomic changes with clinicopathologic parameters.Experimental Design: We screened 97 invasive diploid breast tumors for DNA copy number alterations and changes in transcriptional levels using array comparative genomic hybridization and expression microarrays, respectively.Results: The integrative analysis identified an increase in the overall number of genetic alterations during tumor progression and 15 specific genomic regions with aberrant DNA copy numbers in at least 25% of the patient population, i.e., 1q22, 1q22-q23.1, 1q25.3, 1q32.1, 1q32.1-q32.2, 8q21.2-q21.3, 8q22.3, 8q24.3, and 16p11.2 were recurrently gained, whereas 11q25, 16q21, 16q23.3, and 17p12 were frequently lost (P < 0.01). An examination of the expression patterns of genes mapping within the detected genetic aberrations identified 47 unique genes and 1 Unigene cluster significantly correlated between the DNA and relative mRNA levels. In addition, more malignant tumors with normal gene dosage levels displayed a recurrent overexpression of UBE2C, S100A8, and CBX2, and downregulation of LOC389033, STC2, DNALI1, SCUBE2, NME5, SUSD3, SERPINA11, AZGP1, and PIP.Conclusions: Taken together, our findings suggest that the dysregulated genes identified here are critical for breast cancer initiation and progression, and could be used as novel therapeutic targets for drug development to complement classical clinicopathologic features. Clin Cancer Res; 16(15); 3860-74. ©2010 AACR.

Genomic profiles and CRTC1–MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma

“…This region is also frequently gained in several other types of carcinomas. 40,41 An interesting candidate target gene of these gains is MAFA, an oncogene with transforming properties that is overexpressed in multiple myeloma and a subtype of T-cell lymphoma. 42 We also detected recurrent gains of 8q11.1-q12.2 (harboring the LYN, MOS, and PLAG1 oncogenes) in four high-grade tumors.…”

Comparative Analysis of Transcriptional Gene Regulation Indicates Similar Physiologic Response in Mouse Tissues at Low Absorbed Doses from Intravenously Administered211At

“…The web-based BioArray Software Environment system provided by SCIBLU was used for data preprocessing and quantile normalization of raw signal intensities. Further data processing was performed with Nexus Expression 2.0 (BioDiscovery) as described elsewhere (25).…”

High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma

“…Ubiquitin-conjugating enzyme E2C (UBE2C) belongs to the E2 family, and is involved in mitotic cyclin destruction and cell cycle progression (8). UBE2C has been implicated in the carcinogenesis of certain tumors (9,10), and is overexpressed in various human cancers, including breast, esophageal, colon, lung, liver and ovarian cancers (11)(12)(13)(14)(15)(16).…”