Allelic loss on chromosome 9q is a very frequent event in bladder carcinogenesis. In recent years, efforts have been directed towards identifying the postulated tumour suppressor genes on this chromosome arm by deletion mapping and mutation analysis. However, no convincing candidate genes have been identified. This paper describes the development of chromosome 9q alterations in multiple recurrent superficial bladder cancers of ten patients and shows that loss of heterozygosity (LOH) on this chromosome is almost never the characteristic first step. The regions of loss are multiple and variable in different tumours from the same patient and expand in subsequent tumours. Moreover, the regions of loss vary from patient to patient. It is concluded that even if 9q harbours a bladder cancer gatekeeper gene, it is unlikely that the gene will be identified through LOH analysis alone.
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http://dx.doi.org/10.1002/path.1215 | DOI Listing |
Chromosomal instability (CIN) is common in solid tumours and fuels evolutionary adaptation and poor prognosis by increasing intratumour heterogeneity. Systematic characterization of driver events in the TRACERx non-small-cell lung cancer (NSCLC) cohort identified that genetic alterations in six genes, including FAT1, result in homologous recombination (HR) repair deficiencies and CIN. Using orthogonal genetic and experimental approaches, we demonstrate that FAT1 alterations are positively selected before genome doubling and associated with HR deficiency.
View Article and Find Full Text PDFNature
December 2024
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Anticancer Res
December 2024
Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, U.S.A.;
Blood Adv
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UCSF, San Francisco, California, United States.
Trends Genet
December 2024
Department of Developmental Biology, Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address:
Consensus holds that most cells in the embryo are genetically identical and have healthy genomes. However, embryonic cells with abnormal chromosomes are surprisingly frequent. In a recent publication, de Jaime-Soguero et al.
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