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Pathway-Driven Discovery of Rare Mutational Impact on Cancer

Identifying driver mutation is important in understanding disease mechanism and future application of custom tailored therapeutic decision. Functional analysis of mutational impact usually focuses on the gene expression level of the mutated gene itself. However, complex regulatory network may cause...

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Detalles Bibliográficos
Autores principales: Ahn, TaeJin, Park, Taesung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026869/
https://www.ncbi.nlm.nih.gov/pubmed/24883302
http://dx.doi.org/10.1155/2014/171892
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author Ahn, TaeJin
Park, Taesung
author_facet Ahn, TaeJin
Park, Taesung
author_sort Ahn, TaeJin
collection PubMed
description Identifying driver mutation is important in understanding disease mechanism and future application of custom tailored therapeutic decision. Functional analysis of mutational impact usually focuses on the gene expression level of the mutated gene itself. However, complex regulatory network may cause differential gene expression among functional neighbors of the mutated gene. We suggest a new approach for discovering rare mutations that have real impact in the context of pathway; the philosophy of our method is iteratively combining rare mutations until no more mutations can be added under the condition that the combined mutational event can statistically discriminate pathway level mRNA expression between groups with and without mutational events. Breast cancer patients with somatic mutation and mRNA expression were analyzed by our approach. Our approach is shown to sensitively capture mutations that change pathway level mRNA expression, concurrently discovering important mutations previously reported in breast cancer such as TP53, PIK3CA, and RB1. In addition, out of 15,819 genes considered in breast cancer, our approach identified mutational events of 32 genes showing pathway level mRNA expression differences.
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spelling pubmed-40268692014-06-01 Pathway-Driven Discovery of Rare Mutational Impact on Cancer Ahn, TaeJin Park, Taesung Biomed Res Int Research Article Identifying driver mutation is important in understanding disease mechanism and future application of custom tailored therapeutic decision. Functional analysis of mutational impact usually focuses on the gene expression level of the mutated gene itself. However, complex regulatory network may cause differential gene expression among functional neighbors of the mutated gene. We suggest a new approach for discovering rare mutations that have real impact in the context of pathway; the philosophy of our method is iteratively combining rare mutations until no more mutations can be added under the condition that the combined mutational event can statistically discriminate pathway level mRNA expression between groups with and without mutational events. Breast cancer patients with somatic mutation and mRNA expression were analyzed by our approach. Our approach is shown to sensitively capture mutations that change pathway level mRNA expression, concurrently discovering important mutations previously reported in breast cancer such as TP53, PIK3CA, and RB1. In addition, out of 15,819 genes considered in breast cancer, our approach identified mutational events of 32 genes showing pathway level mRNA expression differences. Hindawi Publishing Corporation 2014 2014-05-04 /pmc/articles/PMC4026869/ /pubmed/24883302 http://dx.doi.org/10.1155/2014/171892 Text en Copyright © 2014 T. Ahn and T. Park. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ahn, TaeJin
Park, Taesung
Pathway-Driven Discovery of Rare Mutational Impact on Cancer
title Pathway-Driven Discovery of Rare Mutational Impact on Cancer
title_full Pathway-Driven Discovery of Rare Mutational Impact on Cancer
title_fullStr Pathway-Driven Discovery of Rare Mutational Impact on Cancer
title_full_unstemmed Pathway-Driven Discovery of Rare Mutational Impact on Cancer
title_short Pathway-Driven Discovery of Rare Mutational Impact on Cancer
title_sort pathway-driven discovery of rare mutational impact on cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026869/
https://www.ncbi.nlm.nih.gov/pubmed/24883302
http://dx.doi.org/10.1155/2014/171892
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