In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 1703-1703
Abstract:
The efficacy of Cetuximab therapy in colorectal cancer patients is limited by the development of therapeutic resistance. The currently known oncogenic ‘driver’ mutations do not fully explain the resistance mechanism of Cetuximab. Currently there are no reports of any studies that have explored new driver mutations in Cetuximab resistance by whole exome sequencing (WES). In this study, we performed WES to identify common genetic factors from twenty-two Cetuximab-sensitive and ten Cetuximab-resistant patients, aiming to discover characteristic genes associated with Cetuximab resistance. For Cetuximab-sensitive patients, the mutation frequency of MUC16, FCGBP, DMBT1 was found to be 100%, 90.91% and 86.36%, respectively. MUC16, PDE4DIP and TACC2 were altered in all 10 Cetuximab-resistant samples. We also discovered there are 151 significantly mutated genes (SMGs) in Cetuximab sensitive group and 37 in the resistant group. CYP4A11 was the most frequently mutated gene in Cetuximab-resistant patients. BCAS1, GOLGA6L1 and WNT16 were found to be the second group of frequently mutated genes which found in to occur at a frequency of 60% in resistant patients. After cosine similarity analysis with 30 known signatures, three mutational signatures (signature a, b and c) were found in all CRC tumors, similar to Signature 1, 5 and 6 in COSMIC, respectively. Gene ontology analysis was performed on SMGs and found twelve enriched GO terms. Four genes are enriched in six specific KEGG pathway groups, such as metabolism of xenobiotics by cytochrome P450, Steroid hormone biosynthesis, retinol metabolism and drug metabolism. In conclusion, we show that the establishment of a WES clinical study of Cetuximab resistance CRC with prospective follow-up of patients can help to identify candidate predictive biomarkers of response. Note: This abstract was not presented at the meeting. Citation Format: Changwen Jing, Ting Wang, Rong Ma, Haixia Cao, EnShun Xu, Zhuo Wang, Siwen Liu, Dan Chen, Junying Zhang, Yang Wu, Yuan Zhang, Ping Ding, Michael Y. Sha, Jianzhong Wu, Jifeng Feng. New genetic variations discovered in KRAS wild-type cetuximab resistant Chinese colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1703.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2019-1703
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2019
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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