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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...

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Autores principales: Kazim, Zakia, Wahabi, Khushnuma, Perwez, Ahmad, Lal, Pawanindra, Rizvi, Moshahid Alam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: West Asia Organization for Cancer Prevention 2019
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.
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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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