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Molecular Approaches Towards the Isolation of Pediatric Cancer Predisposition Genes
Published in John T. Kemshead, Pediatric Tumors: Immunological and Molecular Markers, 2020
The first four small deletion patients identified in our series had a negative family history of 13q- associated Rb. The most recent patient diagnosed as a deletion carrier also apparently had sporadic disease with a unilateral tumor and a negative family history. ESD analysis of the parents showed the father had normal levels, but the mother only had 50% normal ESD activity. In both mother and patient, chromosome analysis revealed a small deletion in 13q14. Detailed ophthalmological analysis of the mother showed no retinal abnormality. This family represents the first recognized instance of transmission of a small chromosome deletion and also the first example of a chromosome deletion carrier without detectable tumor development. Dryja et al.29 have suggested that deletion carriers may only develop unilateral, unifocal disease because the deletion also predisposes to the expression of other recessive lethal genes in the same region. Thus, potential tumor precursor cells are removed from the dividing population of cells in the embryonic retina. The mother in this family might represent the extreme form of this hypothesis with no “transformed” cells surviving development. Alternatively, she could have been a tissue mosaic with the hemopoietic and germ lines carrying the deletion but not retinal cells. Finally, it might be that the deletion in the mother does not include the Rb locus but predisposes to an additional adjacent deletion in the son. The isolation of the Rb gene should allow clarification of this issue.
Microdeletion Syndromes
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
Gopalrao V. N. Velagaleti, Nancy J. Carpenter
No syndrome-specific resources are available for the deletion 1p36 syndrome. However, there are general resources for chromosome abnormalities. Information about the disorder can be obtained by searching databases online through your computer service network and from the following sources: Unique: The largest source of information, mutual support, and self-help to families with children with any rare chromosome disorder.Contact a Family (CaF): Based in London, CaF has information on over 1000 rare syndromes and can put families in touch with each other.Family Village: A global community of disability-related resources.Chromosome deletion outreach: An international support group for families with chromosome abnormalities in U.S.A.Med Help International: An organization helping patients find the highest quality medical information.
The role of BCL-2 family proteins and therapeutic potential of BH3-mimetics in malignant pleural mesothelioma
Published in Expert Review of Anticancer Therapy, 2021
Surein Arulananda, Erinna F Lee, W Douglas Fairlie, Thomas John
A landmark in the field arrived when ABT-199 was tested in a phase I study in patients with refractory chromosome deletion 17p chronic lymphocytic leukemia [70]. The observed complete response rate of 20% and a partial response rate of 59%, translating to a 15-month progression-free survival of 69% was unprecedented in this historically poor prognostic group of patients. This was followed by a phase II study in refractory chromosome deletion 17p chronic lymphocytic leukemia patients with similar outcomes [71]. This led to accelerated FDA approval of the drug in April 2016. The efficacy of this drug was confirmed in the phase III MURANO study in patients with refractory chronic lymphocytic leukemia to Venetoclax plus Rituximab versus Bendamustine plus Rituximab [72]. The 2-year progression-free survival rate was 84.9% in the Venetoclax-Rituximab arm versus 36.3% in the Bendamustine-Rituximab arm with the main toxicities being grade 3 to 4 neutropenia, and to a lesser extent tumor lysis syndrome. Venetoclax is now being trialed in a number of cancers including acute myeloid leukemia and breast cancer [73,74].
Atezolizumab prolongs overall survival over docetaxel in advanced non-small-cell lung cancer patients harboring STK11 or KEAP1 mutation
Published in OncoImmunology, 2021
Wei Nie, Lu Gan, Xin Wang, Kai Gu, Fang-Fei Qian, Min-Juan Hu, Ding Zhang, Shi-Qing Chen, Jun Lu, Shu-Hui Cao, Jing-Wen Li, Yue Wang, Bo Zhang, Shu-Yuan Wang, Chang-Hui Li, Ping Yang, Mi–Die Xu, Xue-Yan Zhang, Hua Zhong, Bao-Hui Han
There were also some limitations to our study. First, the sample size of our study and validation cohorts was moderate, which might limit the power of conclusions. Second, and the results should be considered hypothesis generating rather than hypothesis testing since this was a retrospective study. Third, adverse events in different groups could not be assessed due to insufficient data. Fourth, STK11 and KEAP1 mutations are common in lung adenocarcinoma, but less in squamous NSCLC, especially for STK11. The inclusion of squamous carcinoma may introduce a source of bias. Fifth, STK11 and KEAP1 are located on the end of the short arm of chromosome 19.58,59 Therefore, loss of both genes can occur by deletion of the short arm of this chromosome. Because no copy number variation data was available in this study, we cannot exclude effects of heterozygous loss of one or both genes after chromosome deletion or by loss of heterozygosity. Lastly, we could not get the data about which chemotherapeutic drugs were used in patients before treatment with atezolizumab or docetaxel. Thus, we could not assess whether the absence of response to any chemotherapy could predict the absence (or presence) of response to atezolizumab.
Managing complications secondary to Waldenström’s macroglobulinemia
Published in Expert Review of Hematology, 2021
Ilias Pessach, Meletios A. Dimopoulos, Efstathios Kastritis
In 45%-50% of WM cases, nonspecific chromosomal abnormalities (detected by fluorescence in situ hybridization and/or conventional cytogenetics) are present, with 6q chromosome deletion being the most frequent (30%-60%) but without association with clinical outcomes. Other aberrations that may be seen include 13q deletions, del11q, and trisomy 4; 17p deletions and alterations of the TP53 locus (including mutation, deletion, and copy-neutral loss of heterogeneity) have been associated with shorter progression-free survival (PFS) and overall survival (OS), respectively [13,14]. Lastly, t(11;14) is not found in WM and its presence may help differentiate from IgM myeloma, if MYD88 status is not available and other histology criteria are indeterminate.