China
Africa
Explore chapters and articles related to this topic
Hermann J. Muller (1890–1967)
Published in Krishna Dronamraju, A Century of Geneticists, 2018
With Julian Huxley’s help, Muller obtained a temporary position at the Institute for Animal Genetics at Edinburgh University. He was then 50 years old. Muller attracted several students during that period, including some who became well-known geneticists in their own right, such as Charlotte Auerbach, Guido Pontecorvo, and S.P. Ray Chaudhury. With Pontecorvo, Muller worked out the breakage–fusion–bridge cycle (dicentric chromosome formation), independently of Barbara McClintock, and used it to explain the curious dominant lethals he had observed in large numbers since his X-ray work in 1927. The dicentric chromosomes led to cell death and aborted embryos (Pontecorvo and Muller 1942). With his student S.P. Ray Chaudhury, Muller extended his radiation studies to chronic and acute doses. Another finding was that, for gene mutations, it made no difference whether a dose of 400 R was administered in a few minutes or drawn out over a month-long period. In either case, the mutation rate was the same, confirming Muller’s belief that gene mutations were punctiform events (Muller and Chaudhury 1939). The same observation got him embroiled in a dispute with British radiologists who considered it inappropriate it to extrapolate from flies to humans and that Muller’s view might unnecessarily alarm the public about the uses of radiation.
Dietary Pattern, Genomic Stability and Relative Cancer Risk in Asian Food Landscape
Published in Nutrition and Cancer, 2022
Razinah Sharif, Suzana Shahar, Nor Fadilah Rajab, Michael Fenech
Telomeres consist of a conserved hexanucleotide repeat sequence (TTAGGG) that caps the ends of chromosomes and protects them from recombining with each other and thus preventing chromosomal end-to-end fusions. Degradation of telomeres has been shown to lead to chromosomal instability, via telomere end fusions resulting in generation of abnormal dicentric chromosomes and breakage-fusion-bridge cycles within these abnormal chromosomes (75, 76). This leads to gene amplification and gene dosage imbalance which is an important risk factor for cancer. Accelerated telomere shortening and telomere end fusions can result in a persistent DNA damage response leading to cell cycle arrest and apoptosis. Although telomere shortening has been proposed as one of the fundamental mechanisms that determine chromosomal instability, and increased cancer risk, studies on the relationship between dietary factors and telomere biology have mainly focused on western diets such as the Mediterranean diet which is protective but knowledge remains limited with respect to Asian dietary patterns (77, 78).
Chromosomal 1q21 abnormalities in multiple myeloma: a review of translational, clinical research, and therapeutic strategies
Published in Expert Review of Hematology, 2021
Kamlesh Bisht, Brian Walker, Shaji K. Kumar, Ivan Spicka, Philippe Moreau, Tom Martin, Luciano J. Costa, Joshua Richter, Taro Fukao, Sandrine Macé, Helgi van de Velde
Locus specific FISH and spectral karyotyping of patients with ≥4 copies of 1q21 revealed four types of chromosomal anomalies that distinguish this phenotype, namely, JT1q12 gains, deletion of the receptor chromosome including 17p, insertions into the receptor chromosome, and breakage-fusion-bridge cycle amplifications [2]. Such aberrant chromosomes undergo multiple rounds of breakage and fusion cycles and mitotic segregation errors, which finally result into either whole-chromosome arm or segmental duplications [2,31,44]. The epigenetic factors responsible for driving the pericentromeric heterochromatin de-condensation in MM are still unknown. In solid tumors, aberrant expression of histone lysine demethylase 4A (KDM4A) and hypoxic stress induce aberrant amplification of 1q21 [48,49].
Met inhibitors in the treatment of lung cancer: the evidence to date
Published in Expert Opinion on Pharmacotherapy, 2022
Gerhard Hamilton, Barbara Rath
De novo MET amplification occurs in <1%−5% of NSCLC depending on preselection of the patients, characteristics of the assay, and the cut-point used for defining positivity [24,29,36–39]. MET copy-number increases by polysomy or amplification were also detected following acquired resistance to EGFR TKI therapy in lung cancer. High polysomy of MET indicates the presence of multiple copies of chromosome 7 in tumor cells by gene duplication, via mechanisms such as breakage-fusion-bridge cycles [40–42]. Fluorescence in situ hybridization (FISH) can differentiate between polysomy or amplification by assessment of the ratio of MET/CEP7 (centromeric chromosome 7). In polyploidy the MET/CEP7 ratio remains constant as the number of MET genes increases hand in hand with the number of CEP7 markers but in MET amplification, the MET/CEP7 ratio increases due to the multiple copy numbers of MET genes [43]. Amplification seems to represent a distinct role for MET activation as an oncogenic driver. The MET gene copy-number changes in a continuous manner and defining cutoffs for positivity govern the reported frequency of amplification and the significance as predictive marker for responses to MET inhibition. Differences in thresholds between studies complicate comparisons of outcomes of therapy [44]. For the MET/CEP7 ratio, at low (≥1.8, ≤2.2) and intermediate (>2.2, <5) scores of MET-amplification oncogenic overlap (such as EGFR mutations or ALK fusions), occurred in approximately 50% of cases, but none in the high MET amplification category (MET/CEP7 ≥ 5). In particular, when patients were tested for at least one other oncogenic driver, such as EGFR, KRAS, ALK, ERBB2, BRAF, NRAS, ROS1, and/or RET, concomitant drivers in the low, indeterminate and high categories of MET/CEP7 were 52%, 50%, and 0%, respectively. However, the high MET gene amplification (MET/CEP7 ≥ 5) group representing true MET dependency is very rare, with an incidence of only 0.34% [45].