Chromosome band 17q21 in breast cancer: significant association between beclin 1 loss and HER2/NEU amplification

Tiziana Negri; Eva Tarantino; Marta Orsenigo; James F Reid; Manuela Gariboldi; Milvia Zambetti; Marco A Pierotti; Silvana Pilotti

doi:10.1002/gcc.20798

Chromosome band 17q21 in breast cancer: significant association between beclin 1 loss and HER2/NEU amplification

Genes Chromosomes Cancer. 2010 Oct;49(10):901-9. doi: 10.1002/gcc.20798.

Authors

Tiziana Negri¹, Eva Tarantino, Marta Orsenigo, James F Reid, Manuela Gariboldi, Milvia Zambetti, Marco A Pierotti, Silvana Pilotti

Affiliation

¹ Experimental Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

PMID: 20589936
DOI: 10.1002/gcc.20798

Abstract

Treatment success of breast cancer patients with trastuzumab alone or in combination depends not only on HER2/NEU amplification but also on PTEN and PI3K status and efficient cell death programs. In this pilot study, we found a significant association between loss of beclin 1 and HER2/NEU amplification (both on 17q21) in breast cancers. This finding was confirmed in two public copy number microarray datasets. Furthermore, there is a trend associating beclin 1 loss with TP53 mutations, PI3KCA gene gain, and PTEN mutations. Finally, the observation that beclin 1 gene loss predicted a response to trastuzumab alone or in combination with other drugs is worthy of further confirmation in larger cohorts. Our results suggest that, beclin 1 loss may contribute to genome instability and to a defective autophagy that may lead to tumoral cell death in presence of competent apoptosis or senescence pathways.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis Regulatory Proteins / genetics*
Apoptosis Regulatory Proteins / metabolism
Beclin-1
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Chromosomes, Human, Pair 17 / genetics*
Female
Gene Amplification*
Humans
Immunoenzyme Techniques
Loss of Heterozygosity*
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Mutation / genetics
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
PTEN Phosphohydrolase / genetics
PTEN Phosphohydrolase / metabolism
Prognosis
RNA, Messenger / genetics
Receptor, ErbB-2 / genetics*
Receptor, ErbB-2 / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors / genetics
Transcription Factors / metabolism
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism

Substances

Apoptosis Regulatory Proteins
BECN1 protein, human
Beclin-1
Membrane Proteins
Nuclear Proteins
PI3KCA protein, human
RNA, Messenger
TP53 protein, human
Transcription Factors
Tumor Suppressor Protein p53
ERBB2 protein, human
Receptor, ErbB-2
PTEN Phosphohydrolase
PTEN protein, human