Genetic analysis of KRAS mutation status in metastatic colorectal cancer patients

Zavodna, K; Konečný, M; Krivulcik, T.; Špánik, S.; R, Behulova; Vizvaryova, M; E, Weismanová; Galbavý, Š; Kausitz, J

doi:10.4149/neo_2009_03_275

Cited by 12 publications

(6 citation statements)

References 14 publications

(16 reference statements)

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“…Little data are available on the use of pyrosequencing in clinical practice, whereas some studies have compared PCR/sequencing and DxS [12][13][14][15][16][17]27]. These two methods showed comparable sensitivity in two studies in which small cohorts of patients were analyzed [13,14].…”

Section: Discussionmentioning

confidence: 98%

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Detection of KRAS Mutations in Colorectal Carcinoma Patients with an Integrated PCR/Sequencing and Real-Time PCR Approach

Carotenuto¹,

Roma²,

Rachiglio³

et al. 2010

Pharmacogenomics

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The PCR/sequencing test was able to detect 10% mutant DNA in a background of wild-type DNA. By using this assay, we determined the mutational status of KRAS in 527 out of 540 (97.6%) formalin-fixed paraffin-embedded tissues from mCRC patients. PCR/sequencing was not conclusive in 13 cases, in which low-intensity peaks suggestive of potential mutations were identified. The DxS assay, which showed a sensitivity of 1%, identified mutations in 11 out of 13 inconclusive cases. Interestingly, five of these 11 cases showed high levels of DNA fragmentation. No significant difference was found in the ability of PCR/sequencing and DxS to identify KRAS mutations within 160 cases with more than 30% tumor cells. However, in 24 samples with less than 30% tumor cells, DxS showed an higher sensitivity. In conclusion, our findings suggest that PCR/sequencing can be used for mutational analysis of the majority of tumor samples that have more than 30% tumor cell content, whereas more sensitive and expensive tests should be reserved for inconclusive cases and for samples with a low amount of tumor cells.

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Section: Discussionmentioning

confidence: 98%

“…Few studies have compared the results of the DxS and PCR/sequencing methods in the same cohort of patients with contrasting results [12][13][14][15][16][17].…”

mentioning

confidence: 99%

Detection of KRAS Mutations in Colorectal Carcinoma Patients with an Integrated PCR/Sequencing and Real-Time PCR Approach

Carotenuto¹,

Roma²,

Rachiglio³

et al. 2010

Pharmacogenomics

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“…[61][62][63] Separate studies have also reported that the rate of K-ras mutation is enhanced in CRC patients with lung metastasis 64 and that the presence of K-ras mutations in CRC patients with liver metastasis is predictive of bad prognosis. 65 Analysis of the mutational state of ras genes has proven to be very significant for selection of therapeutic approaches in CRC.…”

Section: Pancreatic Ductal Adenocarcinomamentioning

confidence: 96%

Ras in Cancer and Developmental Diseases

Fernández‐Medarde¹,

Santos²

2011

Genes & Cancer

764

629

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Somatic, gain-of-function mutations in ras genes were the first specific genetic alterations identified in human cancer about 3 decades ago. Studies during the last quarter century have characterized the Ras proteins as essential components of signaling networks controlling cellular proliferation, differentiation, or survival. The oncogenic mutations of the H-ras, N-ras, or K-ras genes frequently found in human tumors are known to throw off balance the normal outcome of those signaling pathways, thus leading to tumor development. Oncogenic mutations in a number of other upstream or downstream components of Ras signaling pathways (including membrane RTKs or cytosolic kinases) have been detected more recently in association with a variety of cancers. Interestingly, the oncogenic Ras mutations and the mutations in other components of Ras/MAPK signaling pathways appear to be mutually exclusive events in most tumors, indicating that deregulation of Ras-dependent signaling is the essential requirement for tumorigenesis. In contrast to sporadic tumors, separate studies have identified germline mutations in Ras and various other components of Ras signaling pathways that occur in specific association with a number of different familial, developmental syndromes frequently sharing common phenotypic cardiofaciocutaneous features. Finally, even without being a causative force, defective Ras signaling has been cited as a contributing factor to many other human illnesses, including diabetes and immunological and inflammatory disorders. We aim this review at summarizing and updating current knowledge on the contribution of Ras mutations and altered Ras signaling to development of various tumoral and nontumoral pathologies.

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“…Several studies demonstrated constitutive activating KRAS, BRAF, and PIK3CA mutations in CRC, with KRAS mutations being most frequent at 27-45 % [ 35 , 47 -50 ]. Interestingly, activating KRAS mutations appear early in the genesis of CRC, with mutations found in adenomatous polyps [ 50 ]. Most activating KRAS mutations exhibit GTPase activity loss combined with GTPase-activating protein insensitivity [ 32 ].…”

Section: Egfr Kras and De Novo Crcmentioning

confidence: 99%