Oncogenic mutations in gastric cancer with microsatellite instability

Corso, Giovanni; Velho, Sérgia; Paredes, Joana; Pedrazzani, Corrado; Martins, Diana; Milanezi, Fernanda; Pascale, Valeria; Vindigni, Carla; Pinheiro, Hugo; Leite, Marina Concli; Marrelli, Daniele; Sousa, Sónia; Carneiro, Fátima; Oliveira, Carla; Roviello, Franco; Seruca, Raquel

doi:10.1016/j.ejca.2010.09.008

Cited by 89 publications

(85 citation statements)

References 45 publications

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“…For oncogenic mutation screening we adopted the method reported in detail by Corso et al 16 Briefly, we analyzed for EGFR mutation the hotspot kinase domain (exons 18, 19, 20, and 21) and the polyadeninde (A13) repeat at the 3 0 -UTR. KRAS mutation analysis comprise codons 12 and 13 and BRAF V600E point mutation.…”

Section: Patient Characteristics and Genomic Dna Extractionmentioning

confidence: 99%

Oncogenic mutations and microsatellite instability phenotype predict specific anatomical subsite in colorectal cancer patients

et al. 2013

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In colorectal cancer (CRC) oncogenic mutations such as KRAS alterations, are considered standard molecular biomarkers that predict the clinical benefit for targeted intervention with epidermal growth factor receptor (EGFR) inhibitors. In addition, these mutations are associated with specific anatomical area in colon tumor development, as BRAF mutations with the microsatellite instability (MSI). In this translational study, we aimed to assess the mutation frequencies of the EGFR (hotspot area and polyadenine deletions A13_del), KRAS, BRAF V600E , and PIK3CA oncogenes in a series of 280 CRC patients. MSI phenotypes are also considered in this series. All patients' clinicopathological data were assessed for statistical analysis and its associations were validated. We verified multiple associations between oncogenic mutations and determined clinicopathological tumor features (1) EGFR A13_deletions are associated with right colon carcinoma (Po0.005), mucinous histotype (P ¼ 0.042), G3 grading (P ¼ 0.024), and MSI status (Po0.005); (2) PIK3CA mutations are related mucinous histotype (P ¼ 0.021); (3) KRAS G12 and KRAS G13 mutations are correlated, respectively, with the left and right colon cancer development (Po0.005), and finally (4) MSI is associated with right colon tumors (Po0.005). Mostly, we verified a higher frequency rate of the KRAS G13 and EGFR A13_del oncogene mutations in right colon cancer; whereas KRAS G12 codon mutation occurs more frequently in left colon cancers. In particular, we assessed that right vs left colon cancer are associated with specific molecular characteristics. These evidences, in association with clinicopathological data, can delineate novel approaches for the CRC classification and targeted intervention.

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Section: Patient Characteristics and Genomic Dna Extractionmentioning

confidence: 99%

Oncogenic mutations and microsatellite instability phenotype predict specific anatomical subsite in colorectal cancer patients

et al. 2013

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“…In re cent ye ars, mo le cu lar ge ne tic stu di es ha ve shown that chan ges in the cell can be one of the ef fec ti ve factors in the mec ha nism of gas tric car ci no gens. [25][26][27] Mo le cu lar ge ne tic al te ra ti ons in gas tric can cer cells, which are de fi ned as ac ti va ti on of on co ge nes and inac ti va ti on of tu mor sup pres si on ge nes, are known as ma in chan ges li ke PTEN ge ne. 28,29 PTEN ge ne is one of the land sca per ge ne pla ying ro les in cell signal cas ca de which has so me as sign ments in PI3K/AKT path way.…”

Section: Discussionmentioning

confidence: 99%

Screening of PTEN Gene Mutations in Gastric Cancer

Yiğin¹,

Cora²,

Acar³

et al. 2014

Turkiye Klinikleri J Med Sci

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“…35 PI3K is a component of the AKT/mTOR signaling pathway that regulates various cellular processes related to tumorigenesis, such as cell proliferation, cell survival, adhesion, motility, and angiogenesis. 36 Gene amplifications, deletions, and somatic missense mutations of the PIK3CA gene have been reported in several cancers including colon, 37 breast, 38 ovary, 39 brain, 40 stomach, 41 lung, 42 and biliary tract cancer. 43 Therefore, mTOR plays a key role in cell growth and homeostasis, and its regulation is frequently altered in human tumors.…”

Section: Commentmentioning

confidence: 99%

Immunohistochemical Expression of Phospho-mTOR Is Associated With Poor Prognosis in Patients With Gallbladder Adenocarcinoma

Leal

García

Sandoval

et al. 2013

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Advanced gallbladder carcinoma (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a central role in cell growth and homeostasis. Its regulation is frequently altered in various tumors and is an attractive target for cancer therapy; however, its status in GBC remains unclear.Objective.-To characterize immunohistochemical expression and prognostic significance of phospho-mTOR in advanced gallbladder carcinoma.Design.-Phospho-mTOR expression was examined by immunohistochemistry in tissue microarrays containing 128 advanced GBCs and 99 cases of chronic cholecystitis, which were divided into 2 groups according to the presence or absence of metaplasia. To evaluate the association of the level of phospho-mTOR expression with clinical variables and patient survival, the advanced GBCs were classified as having low or high expression. Statistical analysis was performed by using a significance level of P , .05, and Kaplan-Meier curves were constructed for survival analysis.Results.-Immunostaining for phospho-mTOR was positive in 82 of 128 tumors (64.1%) and in 24% of chronic cholecystitis cases (16% nonmetaplasia and 32% with metaplasia) (P , .001). Survival analysis indicated that a high phospho-mTOR immunohistochemical expression was associated with poorer prognosis in patients with advanced GBC (P ¼ .02).Conclusions.-Metaplasia is a common finding in chronic cholecystitis and is considered a precursor lesion of dysplasia. Our results suggest that the activation of mTOR occurs very early during the development of GBC, contributing to the carcinogenesis process. PhosphomTOR expression is correlated with poor survival, supporting the potential of mTOR for targeted therapy.

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Oncogenic mutations in gastric cancer with microsatellite instability

Cited by 89 publications

References 45 publications

Oncogenic mutations and microsatellite instability phenotype predict specific anatomical subsite in colorectal cancer patients

Oncogenic mutations and microsatellite instability phenotype predict specific anatomical subsite in colorectal cancer patients

Screening of PTEN Gene Mutations in Gastric Cancer

Immunohistochemical Expression of Phospho-mTOR Is Associated With Poor Prognosis in Patients With Gallbladder Adenocarcinoma

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