Prevalencia y características de mutaciones somáticas del gen KRAS en pacientes chilenos con cáncer colorectal

Hurtado, Claudia; Encina, Gonzalo; Wielandt, Ana María; Zárate, Alejandro; Castro, Magdalena; Carrillo, Katya; Kronberg, Udo; López-Köstner, Francisco

doi:10.4067/s0034-98872014001100007

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…Other studies in Latin America report contrasting frequencies ranging from 13% (Colombia and Venezuela) to 40% (Chile). However, the literature shows that the RAS mutation prevalence usually has a range of 26% to 50% [ 34 – 36 ].…”

Section: Discussionmentioning

confidence: 99%

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KRAS, NRAS, and BRAF mutation prevalence, clinicopathological association, and their application in a predictive model in Mexican patients with metastatic colorectal cancer: A retrospective cohort study

Sánchez-Ibarra¹,

Jiang

Gallegos-Gonzalez³

et al. 2020

PLoS ONE

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Mutations in KRAS, NRAS, and BRAF (RAS/BRAF) genes are the main predictive biomarkers for the response to anti-EGFR monoclonal antibodies (MAbs) targeted therapy in metastatic colorectal cancer (mCRC). This retrospective study aimed to report the mutational status prevalence of these genes, explore their possible associations with clinicopathological features, and build and validate a predictive model. To achieve these objectives, 500 mCRC Mexican patients were screened for clinically relevant mutations in RAS/BRAF genes. Fifty-two percent of these specimens harbored clinically relevant mutations in at least one screened gene. Among these, 86% had a mutation in KRAS, 7% in NRAS, 6% in BRAF, and 2% in both NRAS and BRAF. Only tumor location in the proximal colon exhibited a significant correlation with KRAS and BRAF mutational status (p-value = 0.0414 and 0.0065, respectively). Further t-SNE analyses were made to 191 specimens to reveal patterns among patients with clinical parameters and KRAS mutational status. Then, directed by the results from classical statistical tests and t-SNE analysis, neural network models utilized entity embeddings to learn patterns and build predictive models using a minimal number of trainable parameters. This study could be the first step in the prediction for RAS/ BRAF mutational status from tumoral features and could lead the way to a more detailed and more diverse dataset that could benefit from machine learning methods.

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Section: Discussionmentioning

confidence: 99%

“…and Venezuela) to 40% (Chile). However, the literature shows that the RAS mutation prevalence usually has a range of 26% to 50% [34][35][36]. Previous studies have shown that mutations in KRAS are variable among populations.…”

Section: Plos Onementioning

confidence: 99%

KRAS, NRAS, and BRAF mutation prevalence, clinicopathological association, and their application in a predictive model in Mexican patients with metastatic colorectal cancer: A retrospective cohort study

Sánchez-Ibarra¹,

Jiang

Gallegos-Gonzalez³

et al. 2020

PLoS ONE

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“…CRC develops through a series of somatic gene mutations that promote malignant behavior [2]. These traditional pathway mutations, propagated by long-lived progenitor cells, lead to activation of proliferative signaling pathways, crypt fission, and aberrant glands that progress pathologically from aberrant crypt foci into small adenomatous polyps and ultimately invasive adenocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

The G-protein coupled receptor 56, expressed in colonic stem and cancer cells, binds progastrin to promote proliferation and carcinogenesis

et al. 2017

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Overexpression of human progastrin increases colonic mucosal proliferation and colorectal cancer progression in mice. The G-protein coupled receptor 56 (GPR56) is known to regulate cell adhesion, migration, proliferation and stem cell biology, but its expression in the gut has not been studied. We hypothesized that the promotion of colorectal cancer by progastrin may be mediated in part through GPR56. Here, we found that GPR56 expresses in rare colonic crypt cells that lineage trace colonic glands consistent with GPR56 marking long-lived colonic stem-progenitor cells. GPR56 was upregulated in transgenic mice overexpressing human progastrin. While recombinant human progastrin promoted the growth and survival of wild-type colonic organoids in vitro, colonic organoids cultured from GPR56−/− mice were resistant to progastrin. We found that progastrin directly bound to, and increased the proliferation of, GPR56-expressing colon cancer cells in vitro, and proliferation was increased in cells that expressed both GPR56 and the cholecystokinin-2 receptor (CCK2R). In vivo, deletion of GPR56 in the mouse germline abrogated progastrin-dependent colonic mucosal proliferation and increased apoptosis. Loss of GPR56 also inhibited progastrin-dependent colonic crypt fission and colorectal carcinogenesis in the azoxymethane (AOM) mouse model of colorectal cancer. Overall, we found that progastrin binds to GPR56 expressing colonic stem cells, which in turn promotes their expansion, and that this GPR56-dependent pathway is an important driver and potential new target in colorectal carcinogenesis.

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“…34 Although the genetic term generally leads to understanding cancer as a hereditary disease, this only occurs in a small percentage. In most tumors, the alterations described are only somatic and, therefore, cannot be transmitted to offspring 35,36 so it is important to study mutations linked to cancers. Here we evidence 55 mutations in the 10 HMTs genes studied.…”

Section: Discussionmentioning

confidence: 99%

A Computational Approach to Predict the Role of Genetic Alterations in Methyltransferase Histones Genes With Implications in Liver Cancer

et al. 2023

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Histone methyltransferases (HMTs) comprise a subclass of epigenetic regulators. Dysregulation of these enzymes results in aberrant epigenetic regulation, commonly observed in various tumor types, including hepatocellular adenocarcinoma (HCC). Probably, these epigenetic changes could lead to tumorigenesis processes. To predict how histone methyltransferase genes and their genetic alterations (somatic mutations, somatic copy number alterations, and gene expression changes) are involved in hepatocellular adenocarcinoma processes, we performed an integrated computational analysis of genetic alterations in 50 HMT genes present in hepatocellular adenocarcinoma. Biological data were obtained through the public repository with 360 samples from patients with hepatocellular carcinoma. Through these biological data, we identified 10 HMT genes ( SETDB1, ASH1L, SMYD2, SMYD3, EHMT2, SETD3, PRDM14, PRDM16, KMT2C, and NSD3) with a significant genetic alteration rate (14%) within 360 samples. Of these 10 HMT genes, KMT2C and ASH1L have the highest mutation rate in HCC samples, 5.6% and 2.8%, respectively. Regarding somatic copy number alteration, ASH1L and SETDB1 are amplified in several samples, while SETD3, PRDM14, and NSD3 showed a high rate of large deletion. Finally, SETDB1, SETD3, PRDM14, and NSD3 could play an important role in the progression of hepatocellular adenocarcinoma since alterations in these genes lead to a decrease in patient survival, unlike patients who present these genes without genetic alterations. Our computational analysis provides new insights that help to understand how HMTs are associated with hepatocellular carcinoma, as well as provide a basis for future experimental investigations using HMTs as genetic targets against hepatocellular carcinoma.

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Prevalencia y características de mutaciones somáticas del gen KRAS en pacientes chilenos con cáncer colorectal

Abstract: Prevalencia y características de mutaciones somáticas del gen KRAS en pacientes chilenos con cáncer colorrectalClaudia hurtado 1,a

Cited by 8 publications

References 32 publications

KRAS, NRAS, and BRAF mutation prevalence, clinicopathological association, and their application in a predictive model in Mexican patients with metastatic colorectal cancer: A retrospective cohort study

KRAS, NRAS, and BRAF mutation prevalence, clinicopathological association, and their application in a predictive model in Mexican patients with metastatic colorectal cancer: A retrospective cohort study

The G-protein coupled receptor 56, expressed in colonic stem and cancer cells, binds progastrin to promote proliferation and carcinogenesis

A Computational Approach to Predict the Role of Genetic Alterations in Methyltransferase Histones Genes With Implications in Liver Cancer

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