Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serine/threonine kinase 11 (STK11) is known as a critical tumor-suppressor gene that is frequently mutated in a broad spectrum of human cancers. Among these, the p.F354L mutation of STK11 has been identified in sporadic colon or lung cancer cases. Here, we report the case of a 75-year-old male patient who underwent surgical treatment for multiple tumors of the gastrointestinal system. Genetic mutations were screened in all resected samples, including duodenal high-grade adenoma, gastric high-grade adenoma, rectal adenocarcinoma, and liver metastasis of rectal adenocarcinoma, by next-generation sequencing for mutational hotspots involving 50 oncogenes and tumor suppressor genes. The characteristic hamartomatous polyp of Peutz-Jeghers syndrome was not detected in any tumor specimen. However, all samples as well as the normal rectal mucosa harbored the genetic mutation p.F354L in STK11. In addition, somatic mutations coexisted in the tumor samples, including KRAS p.A146T, TP53 p.G238X, and APC p.T1556fs in the duodenal adenoma; TP53 p.G238Y and APC p.T1556fs in the gastric adenoma; and TP53 p.R282W in the rectal adenocarcinoma and metastatic liver cancer. No somatic mutation was detected in the normal rectal mucosa as a control sample. To our knowledge, this is the first report of an STK11 germline mutation in a patient with multiple tumors of the gastrointestinal tract.
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PMID:STK11 p.F354L Germline Mutation in a Case of Multiple Gastrointestinal Tumors. 3325 Jun 96

In non-small-cell lung cancer (NSCLC), concurrent mutations in the oncogene KRAS and the tumour suppressor STK11 (also known as LKB1) encoding the kinase LKB1 result in aggressive tumours prone to metastasis but with liabilities arising from reprogrammed metabolism. We previously demonstrated perturbed nitrogen metabolism and addiction to an unconventional pathway of pyrimidine synthesis in KRAS/LKB1 co-mutant cancer cells. To gain broader insight into metabolic reprogramming in NSCLC, we analysed tumour metabolomes in a series of genetically engineered mouse models with oncogenic KRAS combined with mutations in LKB1 or p53. Metabolomics and gene expression profiling pointed towards activation of the hexosamine biosynthesis pathway (HBP), another nitrogen-related metabolic pathway, in both mouse and human KRAS/LKB1 co-mutant tumours. KRAS/LKB1 co-mutant cells contain high levels of HBP metabolites, higher flux through the HBP pathway and elevated dependence on the HBP enzyme glutamine-fructose-6-phosphate transaminase [isomerizing] 2 (GFPT2). GFPT2 inhibition selectively reduced KRAS/LKB1 co-mutant tumour cell growth in culture, xenografts and genetically modified mice. Our results define a new metabolic vulnerability in KRAS/LKB1 co-mutant tumours and provide a rationale for targeting GFPT2 in this aggressive NSCLC subtype.
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PMID:The hexosamine biosynthesis pathway is a targetable liability in KRAS/LKB1 mutant lung cancer. 3325 55

Inherited lung cancer risk, particularly in non-smokers, is poorly understood. Genomic and ancestry analysis of 1153 lung cancers from Latin America revealed striking associations between Native American ancestry and their somatic landscape, including tumor mutational burden (TMB), and specific driver mutations in EGFR, KRAS, and STK11. A local Native American ancestry risk score was more strongly correlated with EGFR mutation frequency compared to global ancestry correlation, suggesting that germline genetics (rather than environmental exposure) underlie these disparities.
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PMID:Genetic ancestry contributes to somatic mutations in lung cancers from admixed Latin American populations. 3326 47


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