The gene is frequently mutated and abnormally activated in many cancers，and plays an important role in cancer development. Metabolic reprogramming occurs in malignant tumors，which can be one of the key targets for anti-tumor therapy. gene can regulate lipid metabolism through AKT-mTORC1 single axis or multiple pathways，such as lipid synthesis pathways and degradation pathways. Similarly，lipid metabolism can also modify and activate RAS protein and its downstream signaling pathways. This article overviews the current research progress on the interaction between lipid metabolism and ，to provide insight in therapeutic strategies of lipid metabolism for -driven tumors.
Genes, ras ; Humans ; Lipid Metabolism/genetics* ; Neoplasms/genetics* ; Signal Transduction ; ras Proteins/metabolism*

Adenocarcinoma ; classification ; genetics ; pathology ; Adenocarcinoma, Bronchiolo-Alveolar ; genetics ; pathology ; Exons ; Humans ; Lung Neoplasms ; classification ; genetics ; pathology ; Mutation ; Oncogene Proteins, Fusion ; genetics ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; Receptor, Epidermal Growth Factor ; genetics ; ras Proteins ; genetics

Colorectal Neoplasms ; genetics ; DNA Mutational Analysis ; standards ; Humans ; Mutation ; Proto-Oncogene Proteins B-raf ; genetics ; ras Proteins ; genetics

OBJECTIVE: To investigate the clinical characteristics of RAS gene mutations in patients with acute myeloid leukemia (AML). METHODS: 43 myeloid gene mutations were detected using next-generation sequencing (NGS) in 180 patients with AML who were first diagnosed between May 2011 and February 2021. The molecular and clinical features of RAS gene mutations and their effects on efficacy and survival of patients were retrospectively analyzed. RESULTS: Among 180 AML patients, the proportion of mutations in RAS pathway-related genes were NRAS (14.4%), KRAS (2.2%), FLT3-ITD (13.8%), PTPN11 (7.7%), KIT (5.0%), FLT3-TKD (3.8%) and CBL (2.7%). Seventy-three (40.6%) AML patients had gene mutations associated with the RAS pathway.The number of peripheral blood white blood cells and the proportion of bone marrow primitive juvenile cells in patients with NRAS/KRAS gene mutation were higher than those of patient with RAS wild-type, the difference was statistically significant (P<0.05). NRAS/KRAS gene mutations were significantly associated with the CBL gene mutation(r=0.287). In young AML patients (age <60 years), there were no significant differences in complete response rate (CR), progression-free survival (PFS), and overall survival (OS) between patients with RAS gene mutation and those with wild-type(P>0.05). In elderly AML patients (age≥60 years), PFS and OS in RAS mutants were significantly lower than those in wild-type patients(P<0.05). CONCLUSION In AML patients, RAS gene mutation is relatively common, and RAS gene mutation is associated with clinical characteristics and efficacy of patients, and may be a molecular marker of poor prognosis for elderly AML.
Aged ; Genes, ras ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Nucleophosmin ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; Retrospective Studies ; fms-Like Tyrosine Kinase 3/genetics*

Antineoplastic Agents ; therapeutic use ; Colorectal Neoplasms ; classification ; drug therapy ; genetics ; pathology ; Humans ; Microsatellite Instability ; Mutation ; Polymorphism, Single Nucleotide ; Precision Medicine ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins B-raf ; genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins ; genetics

OBJECTIVEIt is demonstrated that KRAS2, functioning as an oncogene, plays a critical role in carcinogenesis. However, some studies suggest that the wild type KRAS2, located in the region of 12p12.1, takes its effect as a tumor suppressor gene. This study, therefore, is aimed to investigate the loss of heterozygosity (LOH) on chromosome 12p12-13 region in 10 human colon carcinomas.

METHODSLOH analysis of the 12p12-13 region was performed by PCR, using 11 microsatellite markers in 12p12-13 region. The relationships between LOH for each marker and clinical pathologic factors were evaluated.

RESULTSLOH in at least one of the loci in 12p12-13 region was detected in 30% (3/10) of adjacent tissues; the highest frequency of LOH was identified at the locus of D12S1034 in 28.57% (2/7) of adjacent tissues. 60% (6/10) carcinoma tissues were found to have LOH in at least one locus in the same region; the most frequent LOH was found at the loci of D12S1034 and D12S1591, both about 42.86% (3/7). Among all samples, 3 cases were noted to have LOH in both adjacent and tumor tissues, and 3 cases were shown to have LOH only in tumor tissues. Occurrence of LOH was not correlated with sex, age, tumor size and lymph node metastasis.

CONCLUSIONAllelic loss on 12p12-13 region would influence the KRAS2 expression by reducing the gene-dosage in colon carcinogenesis.

Asian Continental Ancestry Group ; genetics ; China ; Chromosomes, Human, Pair 12 ; genetics ; Colonic Neoplasms ; ethnology ; genetics ; Humans ; Loss of Heterozygosity ; Polymerase Chain Reaction ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins ; genetics

PURPOSE: To assess the prevalence of KRAS, BRAF, and TP53 mutations in cases of low-grade and high-grade serous carcinomas and to evaluate the clinical outcomes of these morphologically distinct carcinomas. MATERIALS AND METHODS: Patients with primary invasive serous carcinomas were classified according to the universal grading system. Grade 2 serous tumors were excluded. A total of 100 patients were included for clinical evaluation. Thirty-seven patients, including 20 with low-grade and 17 with high-grade carcinomas, were selected for mutational analysis. RESULTS: The low-grade carcinoma group was characterized by young age and premenopausal period compared with the high-grade carcinoma group, but there were no statistically significant differences in stage, metastasis of lymph node and residual disease. There were no statistically significant differences in survival rates, however, the low-grade carcinoma group showed a trend for improved progression-free survival compared with the high-grade carcinoma group of early stage (p = 0.064). Mutations in KRAS and BRAF were found in 6 (30%) and 2 (10%) patients in the low-grade carcinoma group, respectively, however, they were not found in the high-grade carcinoma group. KRAS and BRAF mutations were mutually exclusive, and both mutations were observed in 40% (8/20). The frequency of TP53 mutations in low-grade and high-grade carcinoma groups were found in 20% (4/20) and 70.6% (12/17), respectively (p = 0.009). CONCLUSION: Low-grade serous carcinoma shows mutation pattern different from that with high-grade carcinoma. As there were no significant differences in stage distribution and survival, especially in advanced stage, we suggest that more studies are needed to segregate these patients into distinct disease entities.
Adult ; Cystadenocarcinoma, Serous/*genetics ; DNA Mutational Analysis ; Female ; Humans ; Middle Aged ; Ovarian Neoplasms/*genetics ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins B-raf/*genetics ; ras Proteins/*genetics

OBJECTIVETo investigate the feasibility of real-time PCR-optimized oligonucleotide probe method for detection of KRAS mutations in lung and colorectal carcinomas, as compared with Sanger sequencing method.

METHODSGenomic DNA was extracted from formalin fixed paraffin embedded samples of 221 lung carcinomas and 131 colorectal carcinomas after tumor cell content assessment and macrodissection. Real-time PCR-optimized oligonucleotide probe method and Sanger sequencing were performed to detect KRAS gene mutations. The frequency of KRAS mutation, mutation types, and their concordance were analyzed.

RESULTSKRAS mutation was detected in 6.3% (14/221) and 4.5% (10/221) of 221 lung cancer samples by using real-time PCR-optimized oligonucleotide probe method and Sanger sequencing, respectively, while in 41.2% (54/131) and 40.5% (53/131) of 131 colorectal cancer samples, respectively. There was no significant correlation between KRAS gene mutations and patients' gender and age (P > 0.05). The positive rate of KRAS codon 12 mutation was significantly higher than that of KRAS codon 13 mutation (P < 0.05). The overall concordance between real-time PCR-optimized oligonucleotide probe method and Sanger sequencing for KRAS mutation detection was 97.4%.

CONCLUSIONReal-time PCR-optimized oligonucleotide probe method provides an alternative method with high consistency and sensitivity as compared to Sanger sequencing in gene mutation detection.

Codon ; Colorectal Neoplasms ; genetics ; DNA Mutational Analysis ; methods ; Female ; Humans ; Lung Neoplasms ; genetics ; Male ; Middle Aged ; Mutation ; Oligonucleotide Probes ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; Real-Time Polymerase Chain Reaction ; methods ; Sensitivity and Specificity ; ras Proteins ; genetics

BACKGROUND AND OBJECTIVERecent studies indicated that Non-small cell lung cancer (NSCLC) patients with mutant K-RAS failed to benefit from adjuvant chemotherapy, and the cancer did not respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). These findings indicated that K-RAS gene status can be a biomarker to predict the sensitivity of EGFR TKIs. The aim of this study is to analyze K-RAS gene mutations with NSCLC patients in Cancer Center of Sun Yet-sen University.

METHODS52 fresh frozen tumor tissues were collected and K-RAS genes were amplified by PCR. Then PCR amplification fragments were sequenced and analyzed.

RESULTSSomatic mutations in the codon 12 of K-RAS gene in tumors were identified from 2 of 52 (3.8%) patients. There were no relationships among K-RAS gene mutations and gender, pathology, smoking, differentiation and stage.

CONCLUSIONThe frequency of K-RAS gene mutations with NSCLC in our center is very low and is similar to that in Asia patients, and is lower than that in Caucasian population.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; genetics ; Female ; Humans ; Lung Neoplasms ; genetics ; Male ; Middle Aged ; Mutation ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins ; genetics

No abstract available.
Alleles ; Chronic Disease ; Gastritis/genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; *Polymorphism, Single Nucleotide ; Stomach Neoplasms/*genetics ; ras Proteins/*genetics