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PTEN Genetic and Epigenetic Alterations Define Distinct Subgroups in North Indian Breast Cancer Patients
BACKGROUND: Breast cancer is a heterogeneous disease that can be subdivided on the basis of histopathological features, genetic alterations, and gene-expression profiles. PTEN gene is considered an established tumor suppressor gene in different types of cancer including breast cancer. However, the r...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
West Asia Organization for Cancer Prevention
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485588/ https://www.ncbi.nlm.nih.gov/pubmed/30678449 http://dx.doi.org/10.31557/APJCP.2019.20.1.269 |
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author | Kazim, Zakia Wahabi, Khushnuma Perwez, Ahmad Lal, Pawanindra Rizvi, Moshahid Alam |
author_facet | Kazim, Zakia Wahabi, Khushnuma Perwez, Ahmad Lal, Pawanindra Rizvi, Moshahid Alam |
author_sort | Kazim, Zakia |
collection | PubMed |
description | BACKGROUND: Breast cancer is a heterogeneous disease that can be subdivided on the basis of histopathological features, genetic alterations, and gene-expression profiles. PTEN gene is considered an established tumor suppressor gene in different types of cancer including breast cancer. However, the role of PTEN alterations in north Indian breast cancer has not been explored especially in defining a group with distinct histological factors. METHODOLOGY: 181 sporadic breast cancer and their adjacent normal tissues were included in the present study. We analyzed methylation and LOH through MS-PCR and microsatellite markers respectively. While, for PTEN protein expression, we used immunohistochemistry. All the molecular findings were correlated with the clinicopathological parameters of the patients to underline clinical relevance. RESULTS: We found that LOH and methylation of the PTEN promoter were significantly associated with loss of PTEN protein expression, while, PTEN mutation was a rare event. Furthermore, out of 46 double hit cases (i.e., having both methylation and LOH), 70% (32/46) cases showed complete loss of PTEN expression (P= 0.0249). Both LOH and PTEN promoter methylation were associated significantly with age and clinical stage, while, methylation and loss of PTEN expression were associated with high grade and Her-2 negativity. In addition, a quadruple (ER/PR/Her-2 and PTEN) negative group with distinct features was found. CONCLUSION: The pattern of PTEN expression and its correlation with the clinical parameters indicates that loss of PTEN expression defines a clinical group with distinct features. Hence, PTEN expression provides differential therapeutic strategies for north Indian breast cancer. |
format | Online Article Text |
id | pubmed-6485588 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | West Asia Organization for Cancer Prevention |
record_format | MEDLINE/PubMed |
spelling | pubmed-64855882019-05-13 PTEN Genetic and Epigenetic Alterations Define Distinct Subgroups in North Indian Breast Cancer Patients Kazim, Zakia Wahabi, Khushnuma Perwez, Ahmad Lal, Pawanindra Rizvi, Moshahid Alam Asian Pac J Cancer Prev Research Article BACKGROUND: Breast cancer is a heterogeneous disease that can be subdivided on the basis of histopathological features, genetic alterations, and gene-expression profiles. PTEN gene is considered an established tumor suppressor gene in different types of cancer including breast cancer. However, the role of PTEN alterations in north Indian breast cancer has not been explored especially in defining a group with distinct histological factors. METHODOLOGY: 181 sporadic breast cancer and their adjacent normal tissues were included in the present study. We analyzed methylation and LOH through MS-PCR and microsatellite markers respectively. While, for PTEN protein expression, we used immunohistochemistry. All the molecular findings were correlated with the clinicopathological parameters of the patients to underline clinical relevance. RESULTS: We found that LOH and methylation of the PTEN promoter were significantly associated with loss of PTEN protein expression, while, PTEN mutation was a rare event. Furthermore, out of 46 double hit cases (i.e., having both methylation and LOH), 70% (32/46) cases showed complete loss of PTEN expression (P= 0.0249). Both LOH and PTEN promoter methylation were associated significantly with age and clinical stage, while, methylation and loss of PTEN expression were associated with high grade and Her-2 negativity. In addition, a quadruple (ER/PR/Her-2 and PTEN) negative group with distinct features was found. CONCLUSION: The pattern of PTEN expression and its correlation with the clinical parameters indicates that loss of PTEN expression defines a clinical group with distinct features. Hence, PTEN expression provides differential therapeutic strategies for north Indian breast cancer. West Asia Organization for Cancer Prevention 2019 /pmc/articles/PMC6485588/ /pubmed/30678449 http://dx.doi.org/10.31557/APJCP.2019.20.1.269 Text en Copyright: © Asian Pacific Journal of Cancer Prevention http://creativecommons.org/licenses/BY-SA/4.0 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License |
spellingShingle | Research Article Kazim, Zakia Wahabi, Khushnuma Perwez, Ahmad Lal, Pawanindra Rizvi, Moshahid Alam PTEN Genetic and Epigenetic Alterations Define Distinct Subgroups in North Indian Breast Cancer Patients |
title | PTEN Genetic and Epigenetic Alterations Define Distinct Subgroups in North Indian Breast Cancer Patients |
title_full | PTEN Genetic and Epigenetic Alterations Define Distinct Subgroups in North Indian Breast Cancer Patients |
title_fullStr | PTEN Genetic and Epigenetic Alterations Define Distinct Subgroups in North Indian Breast Cancer Patients |
title_full_unstemmed | PTEN Genetic and Epigenetic Alterations Define Distinct Subgroups in North Indian Breast Cancer Patients |
title_short | PTEN Genetic and Epigenetic Alterations Define Distinct Subgroups in North Indian Breast Cancer Patients |
title_sort | pten genetic and epigenetic alterations define distinct subgroups in north indian breast cancer patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485588/ https://www.ncbi.nlm.nih.gov/pubmed/30678449 http://dx.doi.org/10.31557/APJCP.2019.20.1.269 |
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