Gene expression in 16q is associated with survival and differs between Sørlie breast cancer subtypes

Abstract

We have investigated the relationship between gene expression and chromosomal positions in 402 breast cancer patients. Using an overrepresentation approach based on Fisher's exact test, we identified disproportionate contributions of specific chromosomal positions to genes associated with survival. Our major finding is that the gene expression in the long arm of chromosome 16 stands out in its relationship to survival. This arm contributes 36 (18%) and 55 (11%) genes to lists negatively associated with recurrence-free survival (set to sizes 200 and 500). This is a highly disproportionate contribution from the 313 (2%) genes in this arm represented on the used Affymetrix U133A and B microarray platforms (Bonferroni corrected Fisher test: P < 2.2 x 10(-16)). We also demonstrate differential expression in 16q across tumor subtypes, which suggests that the ERBB2, basal, and luminal B tumors progress along a high grade-poor prognosis path, while luminal A and normal-like tumors progress along a low grade-good prognosis path, in accordance with a previously proposed model of tumor progression. We conclude that important biological information can be extracted from gene expression data in breast cancer by studying non-random connections between chromosomal positions and gene expression. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

Analysis of copy number changes on chromosome 16q in male breast cancer by multiplex ligation-dependent probe amplification

“…Fifty-three percent of male breast cancer cases lost at least some part of 16q. This is a much lower percentage than previously described for female breast cancer (70% in luminal A tumors, 75% overall in invasive ductal cancer), 3,4,6 especially when considering the high ratio of luminal A tumors in male breast cancer compared with female breast cancer. Most cases of male breast cancer showed at least partial loss of 16q.…”

“…High-grade ductal cancer often has complex changes, typically small regions of gain together with larger regions of loss. [2][3][4][5][6] Genetic alterations on chromosome 16 in male breast cancer are poorly characterized compared with female breast cancer, and only a few studies have been performed 1,7,8 of which the first analyzes only one gene on 16q and the latter studies analyze small series of male breast cancer. These studies report frequent chromosomal imbalances on both the short and long arm of chromosome 16.…”

Gene expression meta-analysis identifies chromosomal regions and candidate genes involved in breast cancer metastasis

“…4a). Loss of 16q is one of the most common observed copy number aberrations in breast cancer [23] and has previously been associated with good prognosis in three studies using LOH [24], gene expression profiling [25], or aCGH [26].…”

“…Only one previous study performed by Wennmalm et al has used genome-wide gene expression data to identify positional effects in metastasis of breast cancer [25]. The major finding in that study is negative association of 16q expression and survival.…”

Loss at 16q22.1 identified as a risk factor for intrahepatic recurrence in hepatocellular carcinoma and screening of differentially expressed genes

“…Previous studies on HCC have mapped recurrent CNAs to chromosomes 1q, 4q, 6p, 8p, 8q, 13q, 16p, 16q, 17p, and 17q, but little is known about their associations with intrahepatic recurrence [5][6][7][8][9][10]. CNAs mapping to chromosome 16 are of particular interest because of overrepresentation in tumors, location of multiple genes implicated in tumor progression [11][12][13], and correlation with unfavorable outcomes in multiple types of cancer [14][15][16][17][18][19][20], with conflicting results [21][22][23][24]. Most notably, losses at 16p and 16q have been associated with the HCC etiology of HBV [7,8].…”