Prostate cancer is a common malignancy that develops by structural mutation(s) and/or other genetic alterations in specific genes.The G to T transversions in codon 12 and C to T transitions in codon 13 of KRAS proto-oncogene are predominant point mutations that occur in about 20% of different cancers in human.
The most frequently mutated oncogene in cancer is KRAS, which uses alternative fourth exons to generate two gene products (KRAS4A and KRAS4B) that differ only in their C-terminal membrane-targeting region<sup>1</sup>.
KRAS2 or TP53 mutations were detected in 13 of 1,098 (1.2%) and 20 of 550 (3.6%) subjects, respectively, 16 of whom developed cancer on average after 18.3 months of follow-up.
The performance of EUS-FNA to diagnose malignancy was similarly improved after the KRAS-mutation assay (negative predictive value increased from 67% to 88%; accuracy increased from 85% to 94%).
Thus, the infusion of CD8+ cells targeting mutant KRAS mediated effective antitumor immunotherapy against a cancer that expressed mutant KRASG12D and HLA-C*08:02.
Lung cancer is the leading cause of cancer related deaths worldwide and mutation activating KRAS is one of the most frequent mutations found in lung adenocarcinoma.
Two hundred sixty-two evaluable, primary, high-risk stage I (grade 3, or aneuploid grade 1 or 2, or clear cell) and stage II-IV EOCs, collected at the University Hospitals Leuven and within the European Organisation for Research and Treatment of Cancer 55971 trial, were genotyped for hotspot mutations in KRAS (COSMIC [Catalogue of Somatic Mutations in Cancer] coverage >97%), BRAF (>94%), NRAS (>97%), PIK3CA (>79%), PTEN, FBXW7 (>57%), AKT2, AKT3, and FOXL2, using Sequenom MassARRAY.
We have developed a single, next-generation sequencing assay to simultaneously evaluate colorectal cancers for mutations in relevant cancer genes (KRAS, NRAS, and BRAF) and for tumor microsatellite instability (MSI).
Other clinicopathological features, such as age, location of the tumor, tumor differentiation, Tumor, Node and Metastases classification, and the Union for International Cancer Control staging, showed no positive relationship with K-ras gene mutations.
Global gene expression analyses of these cell lines reveal that HIF-1α and HIF-2α work together to modulate cancer metabolism and regulate genes signature overlapping with oncogenic KRAS.
The proto-oncogene KRAS belongs among the most frequently mutated genes in all types of cancer and is also very important oncogene related to colorectal tumors.
In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases.
At multivariate analysis, cancer-related survival was associated with Dukes' stage (p<0.0001), CEA level (p=0.02), and mutant circulating KRAS2 (p=0.01).
These results indicate that (a) the HBEC model system is a powerful new approach to assess the contribution of individual and combinations of genetic alterations to lung cancer pathogenesis; (b) a combination of four genetic alterations, including human telomerase reverse transcriptase overexpression, bypass of p16/RB and p53 pathways, and mutant K-RAS(V12) or mutant EGFR, is still not sufficient for HBECs to completely transform to cancer; and (c) EGFR tyrosine kinase inhibitors inhibit the growth of preneoplastic HBEC cells, suggesting their potential for chemoprevention.
We found K-ras gene alteration in 8 lesions (16.0%) out of 50 gastric flat adenomas and no difference in its prevalence between adenoma with or without cancer.
This review covers a brief introduction and summary on various NGS technologies, applications and important findings by NGS in lung cancer advances, including further discoveries in previously known target genes (EGFR, ALK and KRAS), the identification of additional lung cancer mutations and the global coordination of cancer genome studies.
An ¹⁸F-FDG PET/CT in an asymptomatic 74-year-old woman with a thyroid cytology suggestive of malignancy but uncertain about the origin of the tumor revealed an stage IV colon adenocarcinoma with KRAS mutation and multiple metastasis (thyroid, lung, and liver).