Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study

Bazan, Viviana; Agnese, Valentina; Corsale, S; Calò, Valentina; Valerio, Maria Rosaria; Latteri, M.; Vieni, Salvatore; Grassi, Nello; Cicero, Giuseppe; Dardanoni, Gabriella; Rm, Tomasino; Colucci, Giuseppe; Gebbia, Nicola; Russo, Antonio

doi:10.1093/annonc/mdi908

Cited by 74 publications

(59 citation statements)

References 25 publications

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“…A previous report looking at exchange kinetics for G13D HRAS using NMR also found a similar approximately 15-fold increase in nucleotide exchange rate for G13D compared with WT HRAS, indicating that SOS-independent auto-activation may be a general phenomenon for all G13D mutants of RAS-family members (58). The relatively fast exchange kinetics measured for the G13D mutant could contribute to the more aggressive biology of G13D-associated tumors seen in some studies (59), although there are also contexts in which G13D-associated tumors interact favorably with specific treatment regimens (26). We also note that the fast exchange kinetics of G13D may provide more access to the active site for small-molecule inhibitors if compounds with sufficient binding affinity can be developed.…”

Section: Discussionsupporting

confidence: 55%

Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations

Hunter

Manandhar

Carrasco

et al. 2015

Molecular Cancer Research

584

598

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KRAS mutations are the most common genetic abnormalities in cancer, but the distribution of specific mutations across cancers and the differential responses of patients with specific KRAS mutations in therapeutic clinical trials suggest that different KRAS mutations have unique biochemical behaviors. To further explain these high-level clinical differences and to explore potential therapeutic strategies for specific KRAS isoforms, we characterized the most common KRAS mutants biochemically for substrate binding kinetics, intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activities, and interactions with the RAS effector, RAF kinase. Of note, KRAS G13D shows rapid nucleotide exchange kinetics compared with other mutants analyzed. This property can be explained by changes in the electrostatic charge distribution of the active site induced by the G13D mutation as shown by Xray crystallography. High-resolution X-ray structures are also provided for the GDP-bound forms of KRAS G12V, G12R, and Q61L and reveal additional insight. Overall, the structural data and measurements, obtained herein, indicate that measurable biochemical properties provide clues for identifying KRASdriven tumors that preferentially signal through RAF.Implications: Biochemical profiling and subclassification of KRAS-driven cancers will enable the rational selection of therapies targeting specific KRAS isoforms or specific RAS effectors.

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Section: Discussionsupporting

confidence: 55%

Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations

Hunter

Manandhar

Carrasco

et al. 2015

Molecular Cancer Research

584

598

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“…The prognostic value of K-Ras mutations has been demonstrated in case-control studies (Bazan et al, 2005;Conlin et al, 2005;Poehlmann et al, 2007). In our study, although the association between K-Ras mutation status and EFS was limited to stage I-III, we found that mutations at codon 12 of K-Ras were significantly associated with poorer EFS in all stages.…”

Section: Discussionsupporting

confidence: 38%

Somatic Mutations of K-Ras and BRAF in Thai Colorectal Cancer and their Prognostic Value

Chaiyapan¹,

Duangpakdee²,

Boonpipattanapong³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Associations with 12 codon present mucinous type cancer mutations, while mutations in codon 13 are related to non-mucinous cancer, however this type is more aggressive with higher metastatic rate. [16][17][18] A KRAS mutation can be considered as bad prognosis mainly in the codon 13, and is also considered to be a biomarker that predicts the response to therapy through EGFR. 17 The genetic mechanism begins with an inactive mutation of the tumor suppressor gene APC, which is responsible for familial adenomatous polyposis, and approximately 85% of colorectal cancer without hereditary relationship.…”

Section: Epidemiologymentioning

confidence: 99%

Colorectal cancer: a review

et al. 2017

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Colorectal cancer (CCR) is the third most common cancer worldwide in men and women, the second largest cause of death related to cancer, and the main cause of death in gastrointestinal cancer. The risk of developing this cancer is related to bad alimentary habits, smoking, intestinal inflammatory disease, polyps, genetic factors, and aging. Of the patients that are diagnosed with colorectal cancer 90% are older than 50, with a median age of 64 years; however, the disease is more aggressive in patients that are diagnosed at younger ages. According to the American Cancer Association, it was accounted for more than 49,700 deaths in 2015. The goal is to reduce the mortality rate with early diagnosis and treatment. Currently, the survival rate is used to predict a patient’s prognosis. The patient is considered to have a positive familial history if a first-degree relative has been diagnosed with colorectal cancer or colonic polyps before the age of 60, or also if two or more first-degree relatives have been diagnosed with cancer or polyps at any age. There are several methods for detecting colorectal cancer, such as the guaiac test, immunochemical test of stool, DNA stool test, sigmoidoscopy, colonoscopy, and barium enema. The stage in which the cancer is detected determines the prognosis, survival, and treatment of the patient. Provide a review about generalities, genetic basis, risk factors, protective factors, clinical course, diagnostic methods, therapy and survival in colorectal cancer. Conducted research from different databases such as PubMed, Medline, MedScape, on the definition, genetic factors, classification, risk factors, protective factors, diagnostic methods, epidemiology, survival and treatment of colorectal cancer. Articles from 2000 to 2017 were included using the following keywords.

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Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study

Abstract: Specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13 are associated with a worse prognosis in sporadic CRC.

Cited by 74 publications

References 25 publications

Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations

Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations

Somatic Mutations of K-Ras and BRAF in Thai Colorectal Cancer and their Prognostic Value

Colorectal cancer: a review

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