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J Cell Physiol. 2018 Jul;233(7):5170-5179. doi: 10.1002/jcp.26332. Epub 2018 Jan 23.

The 9p21 locus: A potential therapeutic target and prognostic marker in breast cancer.

Author information

1
Department of Modern Sciences and Technologies, Faculty of Medicine Mashhad University of Medical Sciences, Mashhad, Iran.
2
Student Research Committee of Department of modern Sciences and Technology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
3
Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
4
Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
5
Department of Gynecology Oncology, Woman Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
6
Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran.
7
Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
8
Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
9
Brighton and Sussex Medical School, Division of Medical Education, Falmer, Brighton, UK.

Abstract

Breast cancer is an important cause of cancer related mortality in women. Despite extensive efforts to identify valid biomarkers for risk stratification, there are relatively few with proven clinical utility. It is recognized that genetic factors play a major role in determining susceptibility to breast cancer. Recent genome-wide-association-studies and gene expression analysis have demonstrated that a locus on chromosome 9p21, which contains three genes; CDKN2B (encoding p15ink4b), CDKN2A (encoding p16ink4a and p14ARF) and the 3' end of CDKN2BAS (an antisense noncoding RNA in the INK4 locus [ANRIL]) are associated with an increased risk of this malignancy. ANRIL has a post transcriptional modulatory activity, which has been shown to perturb the expression of nearby genes and may play an important role in coordinating tissue remodeling through regulation of cell proliferation, apoptosis, aging, extra-cellular matrix remodeling, and inflammatory response. However, the role of ANRIL is not well understood in breast cancer. Hypermethylation of the p14ARF and p16INK4a genes is found in some tumor types. Nevertheless, further studies are necessary to confirm the clinical utility of these putative markers in risk stratification, or assessing prognosis. In this review, we have summarized the prognostic and therapeutic potential of the p14ARF and p16INK4a genes in patients with breast cancer.

KEYWORDS:

9p21 locus; ANRIL; CDKN2A/B; breast cancer

PMID:
29240242
DOI:
10.1002/jcp.26332
[Indexed for MEDLINE]

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