Molecular analysis of the INK4A and INK4B gene loci in human breast cancer cell lines and primary carcinomas Journal Article

Authors: Bisogna, M.; Calvano, J. E.; Ho, G. H.; Orlow, I.; Cordon-Cardo, C.; Borgen, P. I.; Van Zee, K. J.
Article Title: Molecular analysis of the INK4A and INK4B gene loci in human breast cancer cell lines and primary carcinomas
Abstract: The INK4A and INK4B loci are located at 9p21 and have been implicated in the tumorigenesis of various human malignancies. The INK4A gene encodes two cell cycle regulators, p16(INK4A) and ARF, while INK4B encodes p15(INK4B). Previously, we have shown that the p16(INK4) tumor suppressor was not mutated or deleted in primary breast carcinomas. However, primary and metastatic breast carcinomas exhibited a relative hypomethylation of p16(INK4A), which is associated with expression, compared to normal breast tissue. The present study was conducted to determine if inactivation of p15(INK4B) and INK4A exon 1 beta (ARF) are common events in breast carcinoma. Mutational analysis was performed by PCR-SSCP, and mRNA expression was evaluated by RT-PCR. Methylation-specific PCR was used to determine the methylation status of the p15(INK4B) promoter. Our results demonstrate that the p15(INK4B) gene was altered in 3 (21%) of the 14 breast cell lines; one had a silent mutation and two had homozygous deletion of the gene. None of the cell lines showed methylation of p15(INK4B). TWO (14%) cell Lines had homozygous deletion of INK4A exon Ip. All normal and malignant breast tissue samples were wild-type and non-methylated for p15(INK4B) and wild-type for exon 1 beta. Our results show that these structurally and functionally related genes are not invariably affected together, and the most frequently observed alteration at the INK4A and INK4B loci in breast carcinoma appears to be p16INK4A hypomethylation. (C) 2001 Elsevier Science Inc. All rights reserved.
Keywords: mutational analysis; p16 gene; expression; malignant-melanoma; acute lymphoblastic-leukemia; p16(ink4a); tumor-suppressor; cycle arrest; unrelated proteins; p15(ink4b) genes
Journal Title: Cancer Genetics and Cytogenetics
Volume: 125
Issue: 2
ISSN: 0165-4608
Publisher: Elsevier Science, Inc.  
Date Published: 2001-03-01
Start Page: 131
End Page: 138
Language: English
ACCESSION: WOS:000168236400007
DOI: 10.1016/s0165-4608(00)00367-8
PUBMED: 11369056
Notes: Article; Proceedings Paper -- Presented in part at the 89th and 90th AACR Annual Meeting -- 1998 Mar 28-Apr 1 -- New Orleans, LA -- and 1999 Apr 10-14 -- Philadelphia, PA -- Source: Wos
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MSK Authors
  1. Kimberly J Van Zee
    241 Van Zee
  2. Gay Hui Ho
    5 Ho
  3. Irene Orlow
    191 Orlow
  4. Patrick I Borgen
    232 Borgen
  5. Jacqueline E Calvano
    18 Calvano