Preferential loss of expression of p16(INK4a) rather than p19(ARF) in breast cancer

被引:0
|
作者
Brenner, AJ
Paladugu, A
Wang, H
Olopade, OI
Dreyling, MH
Aldaz, CM
机构
[1] UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CARCINOGENESIS,DIV RES,SMITHVILLE,TX 78957
[2] UNIV CHICAGO,MED CTR,CHICAGO,IL 60637
关键词
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The tumor suppressor p16(INK4a) has been shown to be inactivated in numerous cancer lines and primary tumors. Recently, we reported loss of heterozygosity of the region in which p16(INK4a) is located in more than one-half of primary breast tumors, However, mutational analysis of these same tumors revealed mutation of p16(INK4a) to be infrequent, Other possible modes of inactivation, such as de novo methylation and homozygous deletion, have since been shown to occur in numerous neoplasias. Furthering the complexity of this locus, a transcript overlapping the p16(INK4a) coding sequence and encoding a novel peptide with growth-suppressive activity, p19(ARF), has been described, To clearly elucidate the target of aberrations affecting this subchromosomal region and approximate frequency in breast cancer, we performed a comprehensive study including pld deletion analysis by means of interphase chromosomal fluorescence in situ hybridization, methylation analysis of the first exon encoding p16(INK4a) (exon 1 alpha), mutational analysis of exon 1 beta by single-strand conformational polymorphism analysis of p19(ARF) transcripts, and expression of both alpha and beta transcripts by reverse transcription PCR, Homozygous deletion of p16, as determined by interphase chromosomal fluorescence in situ hybridization, was observed in 3 of 18 (17%) tumors analyzed, whereas de novo methylation of exon 1 alpha was observed in an additional 17% (4 of 23), Reduced expression of p16(INK4a) was observed in 11 tumors (48%), including all those in which homozygous deletion or complete methylation was observed, No mutations of exon 1 beta were detected, and expression of its transcript was variable, with 13% demonstrating decreased expression and 17% demonstrating overexpression, These results further support p16(INK4a) as a target of inactivation in the 9p21 region for breast cancer.
引用
收藏
页码:1993 / 1998
页数:6
相关论文
共 50 条
  • [1] Novel frameshift mutation in the p16/INK4A tumor suppressor gene in canine breast cancer alters expression from the p16/INK4A/p14ARF locus
    Kabir, Farruk M. Lutful
    Agarwal, Payal
    DeInnocentes, Patricia
    Zaman, Jishan
    Bird, Allison Church
    Bird, R. Curtis
    [J]. JOURNAL OF CELLULAR BIOCHEMISTRY, 2013, 114 (01) : 56 - 66
  • [2] Cancer-associated mutations at the INK4a locus cancel cell cycle arrest by p16(INK4a) but not by the alternative reading frame protein p19(ARF)
    Quelle, DE
    Cheng, MG
    Ashmun, RA
    Sherr, CJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (02) : 669 - 673
  • [3] Involvement of the Ink4a gene (p16 and p19arf) in murine tumorigenesis
    Orlow, I
    Rabbani, F
    Chin, L
    Pomerantz, J
    Ligeois, N
    Dudas, M
    Depinho, R
    Cordón-Cardó, C
    [J]. INTERNATIONAL JOURNAL OF ONCOLOGY, 1999, 15 (01) : 17 - 24
  • [4] p16(INK4A) expression in invasive laryngeal cancer
    Hernandez, Brenda Y.
    Rahman, Mobeen
    Lynch, Charles F.
    Cozen, Wendy
    Unger, Elizabeth R.
    Steinau, Martin
    Thompson, Trevor
    Saber, Maria Sibug
    Altekruse, Sean F.
    Goodman, Marc T.
    Powers, Amy
    Lyu, Christopher
    Saraiya, Mona
    [J]. PAPILLOMAVIRUS RESEARCH, 2016, 2 : 52 - 55
  • [5] High frequency of aberrant p16(INK4A) expression in human breast cancer
    Geradts, J
    Wilson, PA
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 1996, 149 (01): : 15 - 20
  • [6] Expression of p16/INK4a in posttransplantation lymphoproliferative disorders
    Martin, A
    Baran-Marzak, F
    El Mansouri, S
    Legendre, C
    Leblond, V
    Charlotte, F
    Davi, F
    Canioni, D
    Raphaël, M
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2000, 156 (05): : 1573 - 1579
  • [7] A NOVEL P16(INK4A) TRANSCRIPT
    MAO, L
    MERLO, A
    BEDI, G
    SHAPIRO, GI
    EDWARDS, CD
    ROLLINS, BJ
    SIDRANSKY, D
    [J]. CANCER RESEARCH, 1995, 55 (14) : 2995 - 2997
  • [8] Loss of p16/INK4A protein expression and methylation of the INK4A gene is a frequent finding in Hodgkin's disease
    Garcia, JF
    Villuendas, R
    Sáez, A
    Sánchez, L
    Martinez, P
    Camacho, FI
    Martínez-Montero, JC
    Piris, MA
    [J]. LABORATORY INVESTIGATION, 1999, 79 (01) : 137A - 137A
  • [9] p16 INK4a and cervical cytology
    Holzman, Jennifer P.
    Killeen, Jeffery
    Kamemoto, Lori
    Wakabayashi, Mark
    Shaha, Steve
    [J]. OBSTETRICS AND GYNECOLOGY, 2007, 109 (04): : 107S - 107S
  • [10] Expression of p16(INK4a) suppresses the unbounded and anchorage-independent growth of a glioblastoma cell line that lacks p16(INK4a)
    Higashi, H
    SuzukiTakahashi, I
    Yoshida, E
    Nishimura, S
    Kitagawa, M
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 231 (03) : 743 - 750