ALK
ALK tyrosine kinase receptor precursor (EC 2.7.10.1) (Anaplastic lymphoma kinase) (CD246 antigen)
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Detailed catalog of lung cancer-associated gene mutations provides valuable information for lung cancer diagnosis and treatment. In China, there has never been a wide-ranging study cataloging lung cancer-associated gene mutations. This study aims to reveal a comprehensive catalog of lung cancer gene mutations in china, focusing on EGFR, ALK, KRAS, HER2, PIK3CA, MET, BRAF, HRAS, and CTNNB1 as major targets. Additionally, we also aim to correlate smoking history, gender, and age distribution and pathological types with various types of gene mutations. A retrospective data acquisition was conducted spanning 6 years (2013-2018) among all patients who underwent lung cancer surgeries not bronchial or percutaneous lung biopsy at three major tertiary hospitals. Finally, we identified 1,729 patients who matched our inclusion criteria. 1081 patients (62.49%) harbored EGFR mutation. ALK ([i]n[/i] = 42, 2.43%), KRAS ([i]n[/i] = 201, 11.62%), CTNNB1 ([i]n[/i] = 28, 1.62%), BRAF ([i]n[/i] = 31, 1.79%), PIK3CA ([i]n[/i] = 51, 2.95%), MET ([i]n[/i] = 14, 0.81%), HER2 ([i]n[/i] = 47, 2.72%), HRAS ([i]n[/i] = 3, 0.17%), and other genes([i]n[/i] = 232, 13.4%). Females expressed 55.38% vs. males 44.62% mutations. Among subjects with known smoking histories, 32.82% smokers, 67.15% non-smokers were observed. Generally, 51.80% patients were above 60 years vs. 48.20% in younger patients. Pathological types found includes LUADs 71.11%, SQCCs 1.68%, ASC 0.75%, LCC 0.58%, SCC 0.35%, ACC 0.17%, and SC 0.06%, unclear 25.19%. We offer a detailed catalog of the distribution of lung cancer mutations. Showing how gender, smoking history, age, and pathological types are significantly related to the prevalence of lung cancer in China.
Keywords
- China
- aging
- gene mutation
- lung cancer
- pathology
- tobacco smoking
During ovarian follicle growth, local cellular interactions are essential for oocyte quality acquisition and successful fertilization. While cumulus cells (CCs) nurture oocytes, they also deliver oocyte-secreted factors (OSFs) that activate receptors on CCs. We hypothesized that disturbance of those interactions contributes to age-related lower reproductive success in women submitted to assisted reproductive technology treatments. Women aged 27-48, without recognized personal reproductive disorder, were enrolled in the study and divided in <35- and ≥35-year-old groups. CCs collected upon follicle aspiration were processed for immunocytochemistry and RNA extraction. The expression patterns of OSF receptors BMPR2, ALK 4, ALK5, and activin receptor-like kinase (ALK6) were studied. Independently of age, receptors were found mostly in the cell periphery. The quantitative assay revealed that in older women, BMPR2, ALK 4, and ALK6 were all significantly decreased, whereas ALK5 was slightly increased. Female age imparts an effect on the expression of OSF receptors in CCs. The findings indicate that reproductive aging affects the local regulation of signaling pathways mediated by BMPR2, ALK6, and ALK4 receptor activation, suggesting their joint involvement.
MeSH Terms
- Adult
- Anaplastic Lymphoma Kinase
- Bone Morphogenetic Protein Receptors, Type I
- Bone Morphogenetic Protein Receptors, Type II
- Cumulus Cells
- Female
- Fertilization in Vitro
- Gene Expression Regulation, Developmental
- Humans
- Middle Aged
- Oocytes
- Ovarian Follicle
- Protein-Serine-Threonine Kinases
- Receptor Protein-Tyrosine Kinases
- Receptor, Transforming Growth Factor-beta Type I
- Receptors, Transforming Growth Factor beta
- Reproductive Techniques, Assisted
Keywords
- Aging
- Cumulus cells
- Female infertility
- Gene expression
- Growth factors
Geriatric glioblastoma (GBM) patients have a poorer prognosis than younger patients, but IDH1/2 mutations (more common in younger patients) confer a favorable prognosis. We compared key GBM molecular alterations between an elderly (age ≥ 70) and younger (18 < = age < = 45) cohort to explore potential therapeutic opportunities. Alterations more prevalent in the young GBM cohort compared to the older cohort (P < 0.05) were: overexpression of ALK, RRM1, TUBB3 and mutation of ATRX, BRAF, IDH1, and TP53. However, PTEN mutation was significantly more frequent in older patients. Among patients with wild-type IDH1/2 status, TOPO1 expression was higher in younger patients, whereas MGMT methylation was more frequent in older patients. Within the molecularly-defined IDH wild-type GBM cohort, younger patients had significantly more mutations in PDGFRA, PTPN11, SMARCA4, BRAF and TP53. GBMs from 178 elderly patients and 197 young patients were analyzed using DNA sequencing, immunohistochemistry, in situ hybridization, and MGMT-methylation assay to ascertain mutational and amplification/expressional status. Significant molecular differences occurred in GBMs from elderly and young patients. Except for the older cohort's more frequent PTEN mutation and MGMT methylation, younger patients had a higher frequency of potential therapeutic targets.
MeSH Terms
- Adult
- Age Factors
- Aged
- Aging
- Biomarkers, Tumor
- Brain Neoplasms
- Cohort Studies
- DNA Methylation
- DNA Mutational Analysis
- ErbB Receptors
- Gene Expression Regulation, Neoplastic
- Glioblastoma
- Humans
- Mutation
- Tumor Suppressor Protein p53
Keywords
- DNA sequencing
- GBM
- mutational analysis