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01-03-2016 | Colorectal Cancer

Mutation Spectra of Common Cancer-Associated Genes in Different Phenotypes of Colorectal Carcinoma Without Distant Metastasis

Authors: Shih-Ching Chang, MD, PhD, Pei-Ching Lin, MD, Jen-Kou Lin, MD, PhD, Chien-Hsing Lin, PhD, Shung-Haur Yang, MD, PhD, Wen-Yi Liang, MD, Wei-Shone Chen, MD, PhD, Jeng-Kai Jiang, MD, PhD

Published in: Annals of Surgical Oncology | Issue 3/2016

Abstract

Background

Colorectal cancer (CRC) is a heterogeneous disease caused by genetic and epigenetic alterations. This study aimed to describe the mutation frequency of 12 genes in different CRC phenotypes.

Methods

Patients who underwent surgery at the Taipei Veterans General Hospital during 2000–2010 for CRC (n = 1249) were enrolled. The endpoint was overall survival. The prognostic value was determined with the log-rank test and Cox regression analysis.

Results

We found 1836 mutations of 12 genes in 997 (79.8 %) tumors. Mutations were most frequently in KRAS (485, 38.8 %), TP53 (373, 29.9 %), APC (363, 29.0 %), and PIK3CA (179, 14.3 %); 137 (11.0 %) cancers had high microsatellite instability (MSI). Women had significantly higher high MSI (14.3 %) and BRAF mutation (6.3 %) frequencies. The abnormal MSI (21.7 %) and KRAS (44.6 %), BRAF (8.6 %), PIK3CA (19.4 %), AKT1 (2.2 %), and TGF - βR (9.6 %) mutation frequencies were significantly higher in proximal colon cancer. The high MSI (35.6 %) and BRAF (20.3 %), TGF - βR (18.6 %), PTEN (5.1 %), and AKT1 (3.4 %) mutation frequencies were significantly higher in 59 (4.7 %) poorly differentiated tumors. The high MSI (21.3 %) and KRAS (51.9 %), BRAF (8.3 %), PIK3CA (25.0 %), AKT1 (4.6 %), and SMAD4 (8.3 %) mutation frequencies were significantly higher in 108 mucinous tumors. TNM stage, lymphovascular invasion, and mucinous histology were significantly associated with patient outcomes in univariate and multivariate analyses. Only NRAS mutation (hazard ratio 1.59, 95 % confidence interval 1.06–2.38) affected patient survival.

Conclusions

Mutational spectra differ significantly between CRC subtypes, implying diverse carcinogenetic pathways. The NRAS mutation is important, despite its low frequency.

Available only for authorised users

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Title: Mutation Spectra of Common Cancer-Associated Genes in Different Phenotypes of Colorectal Carcinoma Without Distant Metastasis
Authors: Shih-Ching Chang, MD, PhD
Pei-Ching Lin, MD
Jen-Kou Lin, MD, PhD
Chien-Hsing Lin, PhD
Shung-Haur Yang, MD, PhD
Wen-Yi Liang, MD
Wei-Shone Chen, MD, PhD
Jeng-Kai Jiang, MD, PhD
Publication date: 01-03-2016
Publisher: Springer International Publishing
Published in: Annals of Surgical Oncology / Issue 3/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-015-4899-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Mutation Spectra of Common Cancer-Associated Genes in Different Phenotypes of Colorectal Carcinoma Without Distant Metastasis

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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