Genomic and transcriptomic differences between lobular and luminal ductal invasive carcinoma

• Published in: Cancer research (Chicago, Ill.) Vol. 69; no. 2_Supplement; p. 2039
• Main Authors: Gruel, N, Raynal, V, Lucchesi, C, Pierron, G, Fourchotte, V, Cottu, P, Sastre-Garau, X, Fourquet, A, Delattre, O, Vincent-Salomon, A
• Format: Journal Article
• Language: English
• Published: 15.01.2009
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.SABCS-2039

Abstract Abstract #2039 Background: Invasive lobular carcinomas (ILCs) of the breast are characterized by morphological and phenotypical features such as small, non cohesive, estrogens receptors positive cells, low proliferation rates with a metastatic spreading in numerous and different unusual metastatic sites as compared to invasive ductal carcinomas (IDCs) (Ferlicot et al, 2004). We have previously shown that ILCs presented the same outcome than IDCs (Sastre-Garau et al, 1996). Beyond E-cadherin genomic inactivation, little is known about the underlying genomic and transcriptomic alterations that may discriminate both subtypes.
 Aims of the study: To get an insight into ILC biological specificities, we performed a combined genomic (aCGH), transcriptomic (Affymetrix U133A+B) and phenotypic analysis of a series of 24 lobular carcinomas and compared it to a series of 41 ER-positive IDCs.
 Results: Analysis of genomic copy number showed that ILCs and IDCs shared gains of the 1q11-q43 region and losses of 16q12.1-q24.2 and 17pter-p13.1 regions. ILCs presented the 22q12-q13 loss but not the 16pter-p11.2 gain and 11q23-q24 loss as observed in IDCs. Eight different regions of high level amplifications were found in 29% of ILC cases (7/24 cases). Only one region of amplification was recurrent and observed in 5 out of 24 tumors (21% of the cases). This recurrent region of amplification was localized on the 11q13.2 region and encompassed the Cyclin D1 (CCND1) and Cortactin (CTTN) genes. ILCs and IDCs had comparable overall survival rates, however, unsupervised hierarchical clustering of transcriptomic data showed that ILCs and IDCs clustered apart. Genes involved in cell adhesion and motility, lipid/fatty transport and metabolism and electron transport were differentially expressed between the two groups.
 Conclusions: This integrated analysis emphasized the biological differences between ILC and IDC and highlighted genes of interest that could be useful for diagnosis, and could be new putative therapeutical targets. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2039.