title: Comprehensive analysis of PTEN status in breast carcinomas.
abstract: PTEN plays a well-established role in the negative regulation of the PI3K pathway, which is frequently activated in several cancer types, including breast cancer. A nuclear function in the maintenance of chromosomal stability has been proposed for PTEN but is yet to be clearly defined. In order to improve understanding of the role of PTEN in mammary tumorigenesis in terms of a possible gene dosage effect, its PI3K pathway function and its association with p53, we undertook comprehensive analysis of PTEN status in 135 sporadic invasive ductal carcinomas. Four PTEN status groups were defined; complete loss (19/135, 14%), reduced copy number (19/135, 14%), normal (86/135, 64%) and complex (11/135, 8%). Whereas the PTEN complete loss status was significantly associated with estrogen receptor (ER) negativity (p=0.006) and in particular the basal-like phenotype (p<0.0001), a reduced PTEN copy number was not associated with hormone receptor status or a particular breast cancer subtype. Overall, PI3K pathway alteration was suggested to be involved in 59% (79/134) of tumors as assessed by human epidermal growth factor receptor 2 overexpression, PIK3CA mutation or a complete loss of PTEN. A complex PTEN status was identified in a tumor subgroup which displayed a specific, complex DNA profile at the PTEN locus with a strikingly similar highly rearranged pan-genomic profile. All of these tumors had relapsed and were associated with a poorer prognosis in the context of node negative disease (p=1.4 × 10(-13) ) thus may represent a tumor subgroup with a common molecular alteration which could be targeted to improve clinical outcome.
authors: INSERM U916 VINCO, University of Bordeaux, Institut Bergonié, Bordeaux, France.
authors: Natalie
authors: N
authors: Jones
authors: Françoise
authors: F
authors: Bonnet
authors: Sana
authors: S
authors: Sfar
authors: Marie
authors: M
authors: Lafitte
authors: Delfine
authors: D
authors: Lafon
authors: Ghislaine
authors: G
authors: Sierankowski
authors: Véronique
authors: V
authors: Brouste
authors: Guillaume
authors: G
authors: Banneau
authors: Christine
authors: C
authors: Tunon de Lara
authors: Marc
authors: M
authors: Debled
authors: Gaëtan
authors: G
authors: MacGrogan
authors: Michel
authors: M
authors: Longy
authors: Nicolas
authors: N
authors: Sevenet
mesh_terms: D000483:Alleles; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism*; D043171:Chromosomal Instability; D002875:Chromosomes / Q000648:ultrastructure; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017354:Point Mutation; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human