Chromosome band 17q21 in breast cancer: significant association between beclin 1 loss and HER2/NEU amplification.
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.
Negri
Tiziana
T
Experimental Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Tarantino
Eva
E
Orsenigo
Marta
M
Reid
James F
JF
Gariboldi
Manuela
M
Zambetti
Milvia
M
Pierotti
Marco A
MA
Pilotti
Silvana
S
D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D000071186:Beclin-1; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D008565:Membrane Proteins; D009687:Nuclear Proteins; D051059:PTEN Phosphohydrolase; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C491997:BECN1 protein, human; C503859:PI3KCA protein, human; C495901:TP53 protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human