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*

Animals ; Genes, BRCA2 ; Genes, erbB-1 ; Genes, erbB-2 ; Genes, p16 ; Genes, p53 ; Genes, ras ; Genetic Predisposition to Disease ; genetics ; Humans ; Pancreatic Neoplasms ; classification ; genetics ; pathology

A large number of data derived from molecular analyses support the hypothesis that human cancer is a genetic disease and a distinct subset of genes have been found to be genetically changed in most tumors. Molecular alterations in pancreatic cancer include: (1) oncogenes such as K-ras, c-myc, c-fos, and c-erbB-2; (2) tumor suppressor genes such as p53, p16, DPC4/SMAD4, and DCC; and (3) growth factors such as EGF, FGF, HGF, PDGF, VEGF, TGF-beta. Genetic alterations of K-ras and p53 are common in human pancreatic cancer, but the occurrence of pancreatic cancer is a multi-step phenomenon in which the accumulation of genetic changes is extremely important.
Epidermal Growth Factor ; genetics ; Fibroblast Growth Factors ; genetics ; Genes, Tumor Suppressor ; Genes, myc ; genetics ; Genes, p16 ; Genes, p53 ; genetics ; Genes, ras ; genetics ; Growth Substances ; genetics ; metabolism ; Humans ; Oncogenes ; genetics ; Pancreatic Neoplasms ; genetics

RASopathies are a group of disorders caused by germline variants of genes involved in RAS/MAPK pathway with overlapping features which may complicate their diagnosis. Since almost all RASopathies are autosomal dominant inherited disorders, the affected families may give birth to multiple children with the disease. Owning to the advance in sequencing technology, the genotype-phenotype correlation of RASopathies has become clearer in recent years, and genetic testing is now available in many places, which make prenatal diagnosis for couples with increased risk possible. For de novo variants of RASopathies, prenatal diagnosis is still difficult as the findings in routine ultrasonography are not specific enough. Nevertheless, certain findings may still be used as clues for prenatal diagnosis. This article overviews the common disorders of RASopathies, with an emphasis on the features that can be used as clues for the prenatal diagnosis of RASopathies.
Female ; Genes, ras ; Humans ; MAP Kinase Signaling System/genetics* ; Pregnancy ; Prenatal Diagnosis

OBJECTIVES: To investigate the mutation rate of the RAS gene and its clinical significance in children with acute lymphoblastic leukemia. METHODS: A retrospective analysis was performed on the medical data of 120 children with newly diagnosed acute lymphoblastic leukemia, who were admitted to the Third Affiliated Hospital of Zhengzhou University from January 2015 to January 2020 and underwent next-generation sequencing. The clinical and molecular features were analyzed. The impact of RAS gene mutation on the overall survival rate was evaluated in these children. RESULTS: Among the 120 children, 35 (29.2%) had RAS gene mutation, 30 (25.0%) had KRAS gene mutation, and 5 (4.2%) had both NRAS and KRAS gene mutations. All NRAS mutations and 71% (25/35) of KRAS mutations were located at the 12th and 13th codons. RAS gene mutation was detected in 35 (33.3%) out of 105 children with B-lineage acute lymphoblastic leukemia, but it was not detected in those with acute T lymphocyte leukemia. Of all the children, 11 (9.2%) were lost to follow-up, and among the 109 children followed up, 16 (14.7%) died. The children with RAS gene mutation had a significantly lower 2-year overall survival rate than those without RAS gene mutation (P<0.05). The prognosis of children with RAS gene mutation combined with WT1 overexpression and WBC>50×10⁹/L at diagnosis was worse (P<0.05). CONCLUSIONS RAS gene mutation is commonly observed in children with B-lineage acute lymphoblastic leukemia and may have an adverse effect on prognosis.
Child ; Genes, ras ; Humans ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis ; Retrospective Studies

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*

OBJECTIVEto map out the frequency and types of K-ras gene mutations present in colorectal and lung cancer patients; to evaluate the clinical applicability of a novel real-time double-loop probe PCR using the ADx-K-ras kit, and to compare its performance with the result by using traditional Sanger DNA sequencing in detection of somatic mutations of the tumor genes.

METHODSa total of 827 formalin-fixed paraffin-embedded (FFPE) blocks including 583 from the colorectal and 244 from the lung cancer patients were assayed. Genomic DNA of the sample tissues was extracted, purified and subjected to PCR amplification of K-ras gene codon 12 and 13 and DNA sequencing was carried on using both the traditional Sanger sequencing method and the ADx's K-ras mutation detection kit, respectively. The mutation rates for K-ras gene at codon 12 and 13, and the mutation frequencies detected by using both methods were analyzed.

RESULTS533 out of 583 (91.4%) colorectal cancer samples and 144 out of 244 lung cancer samples (59.0%) were detected using the traditional Sanger DNA sequencing technique, and 583 out of 583 (100.0%) colorectal plus 244 out of 244(100.0%) lung cancers were detected, respectively by using the ADx-K-ras kit. Of the 583 colorectal cancer samples, 192 (32.9%) showed mutations by using the ADx-K-ras kit in comparing with a result of 160 samples (27.4%) with K-ras gene mutation by using the traditional Sanger DNA sequencing technique. Of the 244 lung cancer samples, 26 (10.7%) showed K-ras gene mutations by using ADx-K-ras kit, while in 144 samples detected by using the traditional Sanger DNA sequencing technique, only 12 samples (8.3%) showed K-ras gene mutations. In colorectal cancer analyzed, GGT→GAT at codon 12 was the most common event with 35.1% (66/188) mutations, followed by GGC→GAC at codon 13 with 26.6% (50/188) and GGT→GTT at codon 12 with 18.6% (35/188), while GGT→GCT at codon12 was the most rare with only 1.6% (3/188) of the total mutation cases. In patients with lung cancer analyzed, GGT→GTT at codon 12 was the most common mutation, accounting for 40.9% (9/22), and GGT→GCT at codon 12 the most rare with only about 4.5% (1/22) of the total mutation cases.

CONCLUSIONSK-ras gene mutations were present in colorectal cases, and significantly more frequent than that in lung cancer. There were significant statistical differences between the two methods. ADx-K-ras real-time PCR showed much higher successful detection rates and mutation ratios compared to Sanger sequencing. As a result, the real-time PCR with ADx-K-ras kit proves to have a good clinical applicability and a strong advantage over the traditional Sanger DNA sequencing. It is a effective and reliable tool for clinical screening of somatic gene mutations in tumors.

Colorectal Neoplasms ; genetics ; Genes, ras ; genetics ; Humans ; Lung Neoplasms ; genetics ; Mutation ; Polymerase Chain Reaction ; methods ; Sequence Analysis, DNA ; methods

OBJECTIVETo investigate the K-ras mutation pattern in six pancreatic cancer cell lines from Chinese patients.

METHODSAll six cell lines were analyzed for mutation in exon 1 of the K-ras gene by polymerase chain reaction (PCR) and direct sequencing.

RESULTSAll 6 pancreatic cancer cell lines had GGT --> GTT mutation at K-ras codon 12 but no mutations at codon 13.

CONCLUSIONThe unique GGT --> GTT mutation at codon 12 plays a potential role in the carcinogenesis of pancreatic cancers in Chinese.

Adenocarcinoma ; genetics ; Asian Continental Ancestry Group ; Cell Line, Tumor ; China ; Codon ; Genes, ras ; genetics ; Humans ; Mutation ; Pancreatic Neoplasms ; genetics

OBJECTIVETo analyze the relationship of K-ras mutation with the development of liver metastasis in colorectal cancer patients and the survival outcomes.

METHODSFrom 2003 to 2008, 300 patients who underwent colorectal cancer surgery in the Department of General Surgery of Zhongshan Hospital, Fudan University were assigned to different groups, according to the diagnosis and follow-up results. The mutation of exon 2 of K-ras was detected in primary paraffin-embedded lesions by PCR and Pyrosequencing. The association of gene mutation with the development of liver metastasis and its prognosis was studied.

RESULTSAmong 300 cases, the mutations of exon 2 were present in 120 cases(40%). The G13D mutation was more common in metachronous metastasis group than that in synchronous group(17.0% vs. 8.0%, P=0.041). Multivariable regression analysis showed that G13D mutation was an independent risk factor(HR=1.108, 95%CI:1.032-5.062, P=0.048) for metachronous metastasis. Patients with mutated K-ras had a poorer overall survival compared to those without mutated K-ras for patients without liver metastasis(median overall, 65 vs. 72 months, P=0.039), and for patients who received metastasis resection(median disease-free survival 18 vs. 24 months, P=0.048). Multivariable analysis showed that K-ras mutation was an independent risk factors of overall survival(HR=1.561, 95%CI:1.022-6.422, P=0.045) in patients without liver metastasis.

CONCLUSIONDetection of K-ras mutation may predict the development of liver metastasis and prognosis.

Aged ; Colorectal Neoplasms ; genetics ; pathology ; Female ; Genes, ras ; genetics ; Humans ; Liver Neoplasms ; genetics ; secondary ; Male ; Mutation ; Prognosis

OBJECTIVETo investigate the role of the epigenetic inactivation of Ras association domain family 2 (RASSF2) in the occurrence and development of prostate cancer by detecting the methylation and protein expression of RASSF2 in the tissues of prostate cancer and prostatic hyperplasia.

METHODSWe obtained genome DNA from 30 formalin-fixed paraffin-embedded specimens of prostate cancer (experimental group) and another 30 of prostatic hyperplasia (control group). We detected the methylation of RASSF2 by methylation-specific PCR (MSP) and its protein expression by immunohistochemistry.

RESULTSThe rates of RASSF2 promoter hypermethylation and the absence of its protein expression were 66.7% (20/30) and 70.0% (21/30) respectively in the experimental group, significantly higher than 6.7% (2/30) and 3.3% (1/30) in the control group (P < 0.05). The promoter hypermethylation of RASSF2 was significantly correlated with the absence of its protein expression (P < 0.05).

CONCLUSIONThe epigenetic inactivation of RASSF2 is involved in the occurrence of prostate cancer, and is expected to be a target of molecular diagnosis and treatment of prostate cancer.

DNA Methylation ; Epigenesis, Genetic ; Genes, ras ; Humans ; Male ; Prostatic Neoplasms ; genetics ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism