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Oncotarget. 2017 Sep 27;8(62):105072-105080. doi: 10.18632/oncotarget.21349. eCollection 2017 Dec 1.

Targeted next generation sequencing in Chinese colorectal cancer patients guided anti-EGFR treatment and facilitated precision cancer medicine.

Author information

1
Department of Medical Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, 266005, China.
2
Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, 266005, China.
3
Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
4
BGI-Qingdao Institute, Qingdao SINO-GERMAN Ecopark, Qingdao, 266555, China.
5
Department of Clinical Laboratory, BGI-Shenzhen, Shenzhen, 518083, China.
6
Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.

Abstract

Objective:

Colorectal cancer (CRC) patients with both RAS and BRAF wild-type tumors determined by non-next generation sequencing (NGS) testing may still not respond due to the presence of additional mutated genes such as PIK3CA or PTEN. In this study, a broad, hybrid capture-based NGS assay was used to identify RAS, BRAF and additional targetable genetic alterations from Chinese CRC tissues.

Methods:

Fifty-seven cases of CRC were enrolled, and all the patients signed the informed consent. In total, 7708 exons of 508 tumor-related genes and 78 introns of 19 frequently rearranged genes were assessed for base substitutions, INDELs, copy number alterations, and gene fusions.

Results:

The study found that 50.9% (29/57) of the tumors harbored KRAS mutations, 3.5% (2/57) harbored NRAS mutations and 3.5% (2/57) harbored BRAF mutations. More specifically, 89.7% (26/29) of RAS mutations were located in codon 12. Except for RAS and RAF, anti-EGFR therapy response genetic mutations in PTEN (n=2) and PIK3CA (n=1) were found in 4.7% (3/64) of the samples. Actionable alterations were found in HER2 (n = 7), CCND2 (n = 2), NF1 (n = 1), and BRCA1 (n = 1).

Conclusions:

Our results illustrated that 82.5% (47/57) of the samples harbored at least one actionable genetic alteration identified by NGS. HER2 amplifications or mutations, which were identified in 12.3% of the tissues, defined a unique molecular subtype of CRC. The study suggests that high-throughput NGS testing in CRC tissues is a comprehensive and efficient genomic profiling assay to guide personalized therapy.

KEYWORDS:

colorectal cancer; genetic alteration; next generation sequencing; personalized therapy; targeted therapy

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