Axin is a recently identified tumor suppressor that plays an important role in liver and colon cancers. To gain further insights into the structure and function of Axin in controlling cell growth, we analyzed 54 colorectal cancer tissues for mutations in AXIN1 gene. We employed PCR amplification with 23 sets of primers against introns that encompassed the whole coding region of AXIN1 followed by single-strand conformation polymorphism (SSCP) analysis. After subcloning and sequencing analysis of the reamplified DNA from the aberrant bands, we found, in addition to 3 silent mutations, 6 missense point mutations in different functionally important regions. The missense mutation rate is hence 11%, suggesting that Axin deficiency may contribute to the onset of colorectal tumorigenesis.
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http://dx.doi.org/10.1002/ijc.11435 | DOI Listing |
BMJ Oncol
December 2023
NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Objective: , a representative tumour suppressor gene with sex bias, is frequently altered in urothelial carcinoma (UC). The specific impacts of mutations on gender-based clinical outcomes in UC remain poorly understood.
Methods And Analysis: We enrolled 2438 patients with UC from seven independent real-world cohorts possessing comprehensive clinical and genomic data.
Acta Pharmacol Sin
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
FMS-like tyrosine kinase-3 (FLT3), a class 3 receptor tyrosine kinase, can be activated by mutations of internal tandem duplication (FLT3-ITD) or point mutations in the tyrosine kinase domain (FLT3-TKD), leading to constitutive activation of downstream signaling cascades, including the JAK/STAT5, PI3K/AKT/mTOR and RAS/MAPK pathways, which promote the progression of leukemic cells. Despite the initial promise of FLT3 inhibitors, the discouraging outcomes in the treatment of FLT3-ITD-positive acute myeloid leukemia (AML) promote the pursuit of more potent and enduring therapeutic approaches. The histone acetyltransferase complex comprising the E1A binding protein P300 and its paralog CREB-binding protein (p300/CBP) is a promising therapeutic target, but the development of effective p300/CBP inhibitors faces challenges due to inherent resistance and low efficacy, often exacerbated by the absence of reliable clinical biomarkers for patient stratification.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, 06536, USA.
To regain infectivity, Trypanosoma brucei, the pathogen causing Human and Animal African trypanosomiasis, undergoes a complex developmental program within the tsetse fly known as metacyclogenesis. RNA-binding protein 6 (RBP6) is a potent orchestrator of this process, however, an understanding of its functionally important domains and their mutational constraints is lacking. Here, we perform deep mutational scanning of the entire RBP6 primary structure.
View Article and Find Full Text PDFAdv Biotechnol (Singap)
June 2024
MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, 510275, China.
Autosomal dominant polycystic kidney disease (ADPKD) is a dominant genetic disorder caused primarily by mutations in the PKD1 gene, resulting in the formation of numerous cysts and eventually kidney failure. However, there are currently no gene therapy studies aimed at correcting PKD1 gene mutations. In this study, we identified two mutation sites associated with ADPKD, c.
View Article and Find Full Text PDFJ Mol Diagn
February 2025
Daiichi Sankyo, Inc., Basking Ridge, New Jersey.
This study demonstrates the analytical and clinical validity of the approved (United States and Japan) plasma-based Guardant360 companion diagnostic (CDx) test for selecting patients with human epidermal growth factor receptor 2 (HER2 [ERBB2])-mutated (HER2m) non-small-cell lung cancer (NSCLC) for trastuzumab deruxtecan (T-DXd) treatment. Concordance between the Guardant360 CDx test and the plasma-based AVENIO ctDNA Expanded Kit Assay (AVENIO), as well as the tissue-based clinical trial assays (CTAs) was investigated. Clinical utility was assessed by comparing T-DXd clinical efficacy results of patients in DESTINY-Lung01/02 who tested positive for HER2 mutations using the Guardant360 CDx test to benchmark efficacy results from DESTINY-Lung01/02.
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