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Sex Chromosome Anomalies
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
L. Hamerton John, A. Evans Jane
Polysomy Y conditions are rare. In total, 12 cases have been reported in the literature; eight 48,XYYY, three 49,XYYYY, and one 49,XXYYY (124). The first case of 48,XYYY reported was a five-year-old boy, ascertained because of psychomotor retardation (136). As with 47,XYY, there is no consistent phenotype. Most of the adults are tall, and have minor malformations such as transverse palmar creases, clinodactyly, and abnormal teeth. Genitalia are normal, but five out of the six adults had hypogonadism with azoospermia. Development was delayed, especially with respect to motor and speech development. IQs were in the low normal range with a range of 60–86. Behavior has been characterized by impulsivity and low frustration tolerance, with occasional aggressive outbursts and poor emotional stability (124).
Molecular Pathologic Diagnostics for Personalized Medicine
Published in Il-Jin Kim, Companion Diagnostics (CDx) in Precision Medicine, 2019
A major advantage of ISH is that it is an in situ method that can provide histological findings. For example, FISH or SISH is recommended for HER2 gene testing in gastric cancer. HER2 amplification is frequently heterogeneous in gastric cancer, and tissue specimens contain many stromal cells and inflammatory cells in addition to carcinoma cells. Therefore, PCR-based methods cannot provide accurate information on HER2 gene amplification status in the specific carcinoma cells. Our group reported that the HER2 gene copy number results determined by real-time PCR are correlated with those by FISH (r = 0.501), which was classified as moderate correlation.12 Dual probes for a target gene sequence and a reference sequence are applied in FISH and SISH methods; this allows researchers or clinicians to distinguish between amplification and polysomy,6 thereby representing a major advantage compared with CISH. SISH and CISH slides are observed using conventional bright-field microscopes, whereas FISH requires the use of a fluorescence microscope in a darkroom.
Novel agents may positively impact chemotherapy and transplantation in subsets of diffuse large B-cell lymphoma
Published in Expert Review of Hematology, 2019
Parastoo B. Dahi, Craig H. Moskowitz, Sergio A. Giralt, Hillard M. Lazarus
In a phase I study of nivolumab in 81 patients with lymphoid malignancies, the objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, DLBCL (n = 11), mycosis fungoides, and peripheral T-cell lymphoma, respectively. Among the four DLBCL patients whose disease exhibited a response, two achieved CR, and two achieved PR. The only two patients who had low-level polysomy of PD-L1/PD-L2 had responses of PR and stable disease. Immunohistochemistry analysis was negative for PD-L1 and PD-L2 for the remaining cases. Durations of response in individual patients ranged from 6.0 to 81 weeks. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2 [81]. Anti-PD-1 and anti-PD-L1 therapy have not produced encouraging results for rel/ref DLBCL. This finding could be explained by a lower prevalence of PD-L1+ DLBCL (11% in 1250 samples) [82].
Genomics in non-adenoid cystic group of salivary gland cancers: one or more druggable entities?
Published in Expert Opinion on Investigational Drugs, 2019
Stefano Cavalieri, Francesca Platini, Cristiana Bergamini, Carlo Resteghini, Donata Galbiati, Paolo Bossi, Federica Perrone, Elena Tamborini, Pasquale Quattrone, Lisa Licitra, Laura Deborah Locati, Salvatore Alfieri
MET gene codifies for the hepatocyte growth factor receptor (HGFR). The activation of this pathway is involved in some type of cancers, notably non-small cell lung cancer (NSCLC) [65,66], and in Hepatocellular carcinoma (HCC) [67]. In a German cohort of 198 non-ACC patients (233 in total, 35 ACC), MET was deleted in only 9% of cases [68]. In the majority of non-ACC (57%), a physiological MET disomy was found. Approximately one third of cases had either a polysomy or an amplification of MET gene. The only two cases bearing MET amplification were one adenocarcinoma NOS and one myoepithelial carcinoma. The activity of several MET inhibitors (e.g. crizotinib, capmatinib, cabozantinib) has been explored in NSCLC. However, due to rarity of MET amplification in salivary gland cancers and its general difficulty to be targeted, this test should be performed only in case of lack of all druggable alterations.
Epidermal growth factor receptor (EGFR)-targeted therapies in mesothelioma
Published in Expert Opinion on Drug Delivery, 2019
Puey Ling Chia, Andrew M. Scott, Thomas John
Many other clinical trials using EGFR therapies in MM have been initiated (Table 3) [16,42,65–68]. Other mechanisms of resistance to EGFR inhibition could be a result of concurrent activation of alternative pathways stimulating receptor tyrosine kinases such as AKT and amplification of mesenchymal-epithelial transition factor (MET) oncogene [69]. Salvi et al postulated that the simultaneous high EGFR and MET polysomy, which is associated with the coexpression of related protein receptors, might have implications for the efficacy of combined anti-EGFR and anti-MET TKI therapies [29]. They found that all the patients with high polysomy on EGFR FISH were shown to have MET gene high polysomy as well. However, this is not surprising given that they are both on chromosome 7. Previous cell line studies have also shown that MM cells can acquire resistance against single agent TKIs by simultaneous activation of both EGFR and MET pathways [69]. Further research will be needed to review potential beneficial therapeutic efficacy with combined EGFR and MET inhibitors.