Molecular spectrum of KRAS, NRAS, BRAF and PIK3CA mutations in Chinese colorectal cancer patients: analysis of 1,110 cases

Zhang, Jing; Zheng, Jianming; Yang, Yinghong; Lu, Junliang; Gao, Jie; Lü, Tao; Sun, Jian; Jiang, Hui; Zhu, Yan; Zheng, Yuhui; Liang, Zhiyong; Liu, Tonghua

doi:10.1038/srep18678

Cited by 100 publications

(122 citation statements)

References 47 publications

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“…Existing data have remained inconclusive. Although better prognosis was reported in breast cancer with PIK3CA mutation, it was an unfavorable prognostic factor for colorectal cancer and NSCLC 14, 24, 25. The coexistence of PIK3CA and other driver genes may affect the analysis of PIK3CA as a prognostic marker.…”

Section: Discussionmentioning

confidence: 97%

Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma

Song

Zhang

2016

Cancer Medicine

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PIK3CA mutation represents a clinical subset of diverse carcinomas. We explored the status of PIK3CA mutation and evaluated its genetic variability, treatment, and prognosis in patients with lung adenocarcinoma. A total of 810 patients with completely resected lung adenocarcinoma were recruited between 2008 and 2013. The status of PIK3CA mutation and other three genes, that is, EGFR mutation, KRAS mutation and ALK fusion were examined by reverse transcription‐polymerase chain reaction (RT‐PCR). Survival curves were plotted with the Kaplan–Meier method and log‐rank for comparison. Cox proportional hazard model was performed for multivariate analysis. Among the 810 patients, 23 cases of PIK3CA mutation were identified with a frequency of 2.8%. There were 14 men and 9 women with a median age of 61 years. Seventeen tumors revealed concurrent gene abnormalities of EGFR mutation (n = 12), KRAS mutation (n = 3), and ALK fusion (n = 2). Seven patients with EGFR & PIK3CA mutations recurred and administrated of EGFR‐TKIs yielded a median progression free‐survival of 6.0 months. Among four eviromous‐treated patients, stable disease was observed in three patients with a median Progression‐free survival (PFS) of 3.5 months. Patients with and without PIK3CA mutation had different overall survivals (32.2 vs. 49.6 months, P = 0.003). Multivariate analysis revealed that PIK3CA mutation was an independent predictor of poor overall survival (HR = 2.37, P = 0.017). The frequency of PIK3CA mutation was around 2.8% in the Chinese patients of lung adenocarcinoma. PIK3CA mutation was associated with reduced PFS of EGFR‐TKIs treatment and shorter overall survival.

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Section: Discussionmentioning

confidence: 97%

Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma

Song

Zhang

2016

Cancer Medicine

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“…KRAS mutation prevalence in cholangiocarcinoma ranged from 16% to 38%. [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] …”

Section: Frequency Of Ras Mutation In Gastrointestinal Cancermentioning

confidence: 99%

Frequency of RAS Mutations (KRAS, NRAS, HRAS) in Human Solid Cancer

Kodaz

2017

EJMO

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T he RAS oncogene affects numerous cellular functions, including growth, proliferation, apoptosis, migration, division, and differentiation of the cells. It has 3 known isoforms: Harvey-RAS (HRAS), Kirsten-RAS (KRAS), and neuroblastoma-RAS (NRAS). RAS has an intrinsic GTPase activity; it encodes proteins binding the guanine nucleotides. KRAS and HRAS were discovered in studies conducted on cancer-causing viruses. Retroviral oncogenes related to murine sarcoma virus genes (Kristen rat sarcoma virus and Harvey rat sarcoma virus) were discovered in 1982. These 2 oncogenes are similar to human KRAS. Approximately 30% of all human cancers have RAS gene involvement. Mutations in KRAS account for about 85% of all RAS mutations in human tumors, NRAS for about 11% to 15%, and HRAS for about 1%. Frequency of RAS mutation in intracranial tumorsGliomas constitute 80% of malignant brain tumors. RAS mutations are very rare in malignant gliomas; no RAS mutation was found in a study in which 30 glioblastoma multiforme (GBM) patients were evaluated. The frequency of NRAS mutation was 2.1% in another study, although KRAS and HRAS mutations were not detected. It was reported that RAS mutation frequency was 12% in a study of isocitrate-dehydrogenase 1-mutant malignant glioma. RAS genes were studied in 21 cases of glioblastoma multiforme, 4 cases of fibrillary astrocytoma, 4 cases of anaplastic astrocytoma, and 15 normal specimens. RAS mutation was de-RAS oncogene affects numerous cellular functions including growth, proliferation, apoptosis, migration, division and differentiation of the cells. It has 3 known isoforms as Harvey-RAS (HRAS), Kirsten -RAS (KRAS) and Neuroblastoma-RAS (NRAS). RAS has an intrinsic GTPase activity. It encodes proteins binding the guanine nucleotides. KRAS and HRAS were discovered in studies carried out on viruses leading to cancer. Retroviral oncogenes related to murine sarcoma virus genes (Kristen Rat Sarcoma Virus and Murine Sarcoma Virus) were discovered in 1982. These two oncogenes are similar to human KRAS. Approximately 30% of all human cancers have ras genes. Mutations in KRAS account for about 85% for all RAS mutations in human tumors, NRAS is about 11-15%, and HRAS is about 1%.

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“…Zhang et al have reported differences in the genetic profiles of KRAS, NRAS, PIK3CA, and BRAF at mutation hotspots between CRC patients from China and those from Western countries. The rate of these mutations in Arab patients with CRC is not well defined (9). The evaluations of the rates of these mutations in Arab population with CRC have been limited to few mutations including KRAS and BRAF (19,20).…”

Section: Introductionmentioning

confidence: 99%

“…Gene mutation and defective cell regulation are important processes in the development of CRC (6). Accumulation of these mutations, including mutations in KRAS, NRAS, BRAF and PIK3CA, activate multiple signaling pathways, such as RAS-RAF-MAPK and PI3K-PTEN-AKT, that play a major role in regulating cell proliferation, angiogenesis, cell motility and apoptosis (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern

Al-Shamsi¹,

Jones²,

Fahmawi³

et al. 2016

J. Gastrointest. Oncol.

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Background: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. Methods: Arab patients from the Arab Gulf region and a population of age-and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed. The mutation rates of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were recorded, along with clinicopathological features. Other somatic mutation and their rates were also identified. Fisher's exact test was used to determine the association between mutation status and clinical features. Results: A total of 198 cases were identified; 99 Arab patients and 99 Western patients. Fifty-two point seven percent of Arab patients had stage IV disease at initial presentation, 74.2% had left-sided tumors.Eighty-nine point two percent had tubular adenocarcinoma and 10.8% had mucinous adenocarcinoma. The prevalence rates of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations in Arab population were 44.4%, 4%, 4%, 13.1%, 52.5%, 27.3%, 2% and 3% respectively. Compared to 48.4%, 4%, 4%, 12.1%, 47.5%, 24.2%, 11.1% and 0% respectively in matched Western population. Associations between these mutations and patient clinicopathological features were not statistically significant.Conclusions: This is the first study to report comprehensive hotspot mutations using NGS in Arab patients with CRC. The frequency of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation.

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Molecular spectrum of KRAS, NRAS, BRAF and PIK3CA mutations in Chinese colorectal cancer patients: analysis of 1,110 cases

Cited by 100 publications

References 47 publications

Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma

Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma

Frequency of RAS Mutations (KRAS, NRAS, HRAS) in Human Solid Cancer

Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern

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