Transcription profiling of human ductal and lobular breast cancers with familial or Cowden disease history

A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net) | 74 samples on Affymetrix HG-U133 Plus 2.0 GeneChips arrays for 74 patients. 5 samples on CGH CIT v7 | Breast carcinoma is the main malignant tumor occurring in patients with Cowden disease, a cancer prone syndrome caused by germline mutation of the tumor suppressor gene PTEN. To better understand this disease, we have performed a transcriptomic study of three Cowden disease breast carcinomas included in a panel of 74 familial breast cancers. Unsupervised clustering of these 74 tumors followed the intrinsic gene classification of breast cancer except for a group of five tumors that included the three Cowden tumors. The gene expression profile of the Cowden tumors shows considerable overlap with that of a breast cancer subgroup known as molecular apocrine breast carcinoma, which is suspected to have increased androgenic signaling and shows frequent ERBB2 amplification. A histological and immunohistochemical study performed on 13 additional cases of Cowden disease breast carcinomas, for which RNA was not available, showed that they have apocrine histological features and express GGT1, a marker of molecular apocrine breast carcinoma. These data suggest that activation of the ERBB2-PI3K-AKT pathway by loss of PTEN at early stages of tumorigenesis promotes the formation of breast tumors with apocrine features. | Submitter : Renaud Schiappa [e-mail] | Project leader : Michel Longy [e-mail]