Preferential loss of expression of p16INK4a rather than p19ARF in breast cancer

Andrew Brenner, Abhaya Paladugu, Hui Wang, Olufunmilayo I. Olopade, Martin H. Dreyling, C. Marcelo Aldaz

Research output: Contribution to journalArticle

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Abstract

The tumor suppressor p16INK4a has been shown to be inactivated in numerous cancer lines and primary tumors. Recently, we reported loss of heterozygosity of the region in which p16INK4a is located in more than one-half of primary breast tumors. However, mutational analysis of these same tumors revealed mutation of p16INK4a 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 p16INK4a coding sequence and encoding a novel peptide with growth-suppressive activity, p19ARF, 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 p16 deletion analysis by means of interphase chromosomal fluorescence in situ hybridization, methylation analysis of the first exon encoding p16INK4a (exon 1α), mutational analysis of exon 1β by single-strand conformational polymorphism analysis of p19ARF transcripts, and expression of both a and β 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 Iα was observed in an additional 17% (4 of 23). Reduced expression of p16INK4a was observed in 11 tumors (48%), including all those in which homozygous deletion or complete methylation was observed. No mutations of exon 1β were detected, and expression of its transcript was variable, with 13% demonstrating decreased expression and 17% demonstrating overexpression. These results further support p16INK4a as a target of inactivation in the 9p21 region for breast cancer.

Original languageEnglish (US)
Pages (from-to)1993-1998
Number of pages6
JournalClinical Cancer Research
Volume2
Issue number12
StatePublished - Dec 1996
Externally publishedYes

Fingerprint

Breast Neoplasms
Exons
Methylation
Neoplasms
Interphase
Fluorescence In Situ Hybridization
Mutation
Loss of Heterozygosity
Gene Expression Profiling
Reverse Transcription
Polymerase Chain Reaction
Peptides
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Brenner, A., Paladugu, A., Wang, H., Olopade, O. I., Dreyling, M. H., & Aldaz, C. M. (1996). Preferential loss of expression of p16INK4a rather than p19ARF in breast cancer. Clinical Cancer Research, 2(12), 1993-1998.

Preferential loss of expression of p16INK4a rather than p19ARF in breast cancer. / Brenner, Andrew; Paladugu, Abhaya; Wang, Hui; Olopade, Olufunmilayo I.; Dreyling, Martin H.; Aldaz, C. Marcelo.

In: Clinical Cancer Research, Vol. 2, No. 12, 12.1996, p. 1993-1998.

Research output: Contribution to journalArticle

Brenner, A, Paladugu, A, Wang, H, Olopade, OI, Dreyling, MH & Aldaz, CM 1996, 'Preferential loss of expression of p16INK4a rather than p19ARF in breast cancer', Clinical Cancer Research, vol. 2, no. 12, pp. 1993-1998.
Brenner A, Paladugu A, Wang H, Olopade OI, Dreyling MH, Aldaz CM. Preferential loss of expression of p16INK4a rather than p19ARF in breast cancer. Clinical Cancer Research. 1996 Dec;2(12):1993-1998.
Brenner, Andrew ; Paladugu, Abhaya ; Wang, Hui ; Olopade, Olufunmilayo I. ; Dreyling, Martin H. ; Aldaz, C. Marcelo. / Preferential loss of expression of p16INK4a rather than p19ARF in breast cancer. In: Clinical Cancer Research. 1996 ; Vol. 2, No. 12. pp. 1993-1998.
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