Analysis of genetic and epigenetic processes that influence p14ARF expression in breast cancer.
The INK4a/ARF locus encodes two unrelated cell cycle-regulatory proteins that both function in tumor suppression, p16INK4a and p14ARF. In human tumors including breast cancer, alterations affecting selectively p14ARF have been poorly analysed. We have performed a comprehensive analysis of the inactivation mechanisms (mutation, homozygous and hemizygous deletion, and promoter hypermethylation) in a large series of 100 primary breast carcinomas. RT-PCR showed expression variable of the p14ARF transcript, with 17% demonstrating overexpression and 26% demonstrating decreased expression. No detectable alterations were observed in the majority of cases with overexpressed p14ARF mRNA, but 77% of tumors with decreased expression presented at least one of these genetic/epigenetic alterations. Nevertheless, a statistically significant correlation was observed between decreased p14ARF expression and several poor prognostic parameters.
Silva
J
J
Department of Medical Oncology, Clínica Puerta de Hierro, E-28035-Madrid, Spain.
Domínguez
G
G
Silva
J M
JM
García
J M
JM
Gallego
I
I
Corbacho
C
C
Provencio
M
M
España
P
P
Bonilla
F
F
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D019175:DNA Methylation; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020868:Gene Silencing; D019942:Genes, p16; D006801:Humans; D019656:Loss of Heterozygosity; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion
D019941:Cyclin-Dependent Kinase Inhibitor p16; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm