Comparative expressed sequence hybridisation revealed distinct chromosomal regions of differential gene expression in breast cancer subtypes
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KeywordsChromosomal Region Differential Gene Expression Invasive Ductal Carcinoma Invasive Lobular Carcinoma Breast Cancer Subtype
A recently developed expression profiling technique, termed comparative expressed sequence hybridisation (CESH), was applied for the study of lymph-node negative breast cancer. CESH allows global detection of chromosomal regions with differential gene expression in a way similar to that of comparative genomic hybridisation . Using CESH, we compared gene expression patterns between three different breast cancer subtypes: invasive lobular carcinoma (ILC), poorly differentiated invasive ductal carcinoma ERBB2-positive (ERBB2-positive IDC) and poorly differentiated invasive ductal carcinoma ERBB2-negative (ERBB2-negative IDC).
We intended to investigate whether different morphological breast cancer subtypes are characterised by distinct gene expression patterns. Furthermore, we aimed to identify chromosomal regions that harbour genes with potential significance in the underlying biological behaviour of these subtypes.
Total RNA was extracted from 24 frozen tissue blocks representing eight ILC cases, eight ERBB2-positive IDC cases and eight ERBB2-negative IDC cases. Reverse-transcribed RNA (cDNA) from four cases of the same subtype was pooled, resulting in the formation of two cDNA pools per subtype. First, both cDNA pools of the same subtype were paired with each other. Second, cDNA pools of different subtypes were compared.
Comparing cDNA pools of the same subtype showed no significant differences in gene expression profiling. Most strikingly, CESH was able to discriminate ILC from poorly differentiated IDC by three differentially expressed regions, including relative overexpression at 8p21-p22 and relative underexpression at 8q13-q23 and at 16q22. Collation of all CESH data led to the identification of an ERBB2 signature, comprising relative overexpression at 3q24-q26.3, 17q12-q21 and 20q12-q13.1 and relative underexpression at 8q24.3.
Interpretation and conclusion
CESH has proved useful for the study of lymph-node-negative breast cancer. It highlights regions of differential gene expression that are selectively associated with breast cancer subtypes and supports the hypothesis that ERBB2-positive IDC is a distinct disease entity. Moreover, CESH was able to identify an ERBB2 signature, comprising four chromosomal regions harbouring genes with potential significance in the aggressive behaviour of ERBB2-positive disease.
- 1.Lu YJ, Williamson D, Clark J, Wang R, Tiffin N, Skelton L, Gordon T, Williams R, Allan B, Jachman A, et al: Comparative expressed sequence hybridization to chromosomes for tumor classification and identification of genomic regions of differential gene expression. Proc Natl Acad Sci USA. 2001, 98: 9197-9202. 10.1073/pnas.161272798.CrossRefPubMedPubMedCentralGoogle Scholar