Low frequency KRAS mutations in colorectal cancer patients and the presence of multiple mutations in oncogenic drivers in non-small cell lung cancer patients

Autor: Wei Zhu, Susana Korolevich, Chris Morehouse, Yi Gu, Xiaoxiao Ge, Christine Kiefer, Brandon W. Higgs, Philip Brohawn, Kim Lehmann, Zheng Liu, Liyan Jiang, Dan Sui, Xinying Su, Meggan Czapiga, Yihong Yao, Jiaqi Huang
Rok vydání: 2013
Předmět:
Male
Cancer Research
Lung Neoplasms
Oncogene Proteins
Fusion
Colorectal cancer
DNA Mutational Analysis
medicine.disease_cause
Bioinformatics
Exon
Gene Frequency
oncogene
Carcinoma
Non-Small-Cell Lung
Anaplastic lymphoma kinase
Anaplastic Lymphoma Kinase
Child
In Situ Hybridization
Fluorescence
Medicine(all)
Aged
80 and over
Sanger sequencing
Mutation
Middle Aged
Proto-Oncogene Proteins c-met
ErbB Receptors
symbols
Female
KRAS
Colorectal Neoplasms
Adult
Adolescent
colorectal cancer
Ultradeep sequencing
Biology
Proto-Oncogene Proteins p21(ras)
Young Adult
symbols.namesake
Cell Line
Tumor
Proto-Oncogene Proteins
Genetics
medicine
Humans
Lung cancer
low frequency mutations
Molecular Biology
non-small cell lung cancer
Aged
Oncogene
Receptor Protein-Tyrosine Kinases
HCT116 Cells
medicine.disease
respiratory tract diseases
ras Proteins
Cancer research
Zdroj: Cancer Genetics. 206:330-339
ISSN: 2210-7762
DOI: 10.1016/j.cancergen.2013.09.004
Popis: Intratumor heterogeneity can confound the results of mutation analyses in oncodriver genes using traditional methods thereby challenging the application of targeted cancer therapy strategies for patients Ultradeep sequencing can detect low frequency and expanded clonal mutations in primary tumors to better inform treatment decisions. KRAS coding exons in 61 treatment-naive colorectal cancer (CRC) tumors and KRAS , EGFR , ALK , and MET in lung tumors from three Chinese non-small cell lung cancer (NSCLC) patients were sequenced using ultradeep sequencing methods. Forty-one percent of CRC patients (25/61) harbored mutations in the KRAS active domain, eight of which (13%) were not detected by Sanger sequencing. Three (of eight) had frequencies less than 10% and one patient harbored more than one mutation. Low frequency KRAS active (G12R) and EGFR kinase domain mutations (G719A) were identified in one NSCLC patient. A second NSCLC patient showed an EML4 - ALK fusion with ALK , EGFR , and MET mutations. A third NSCLC patient harbored multiple low frequency mutations in KRAS , EGFR , and MET as well as ALK gene copy number increases. Within the same patient, multiple low frequency mutations occurred within a gene. A complex pattern of intrinsic low frequency driver mutations in well-known tumor oncogenes may exist prior to treatment, resulting in resistance to targeted therapies. Ultradeep sequencing can characterize intratumor heterogeneity and identify such mutations to ultimately affect treatment decisions.
Databáze: OpenAIRE
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