NDLI: Genetic screening in patients with Retinoblastoma in Israel

Content Provider	Springer Nature Link
Author	Sagi, Michal Frenkel, Avishag Eilat, Avital Weinberg, Naomi Frenkel, Shahar Pe’er, Jacob Abeliovich, Dvorah Lerer, Israela
Copyright Year	2015
Abstract	Retinoblastoma (Rb) is a childhood tumor (~1 in 20,000 live births) developing in the retina due to mutations in the RB1 gene. Identification of the oncogenic mutations in the RB1 gene is important for the clinical management and for genetic counseling to families with a child or a parent affected with the tumor. Here we present our experience in detecting the pathogenic mutations in blood samples, from 150 unrelated Rb patients and highlight the relevant counseling issues. Mutation screening in the RB1 gene was based on Sanger sequencing, mosaicism of recurrent CpG transition mutations was detected by allele specific PCR and multiplex ligation dependent probe amplification for detecting of large deletions/duplications. The overall detection rate of mutations in our cohort was 55 % (82/150). In the familial cases it was 100 % (17/17), in bilateral and unilateral-multifocal sporadic cases 91 % (50/55), and in the unilateral sporadic cases 19 % (15/78). Nonsense mutations and small deletions or insertions that results in transcripts with premature termination codons that are subject to nonsense mediated decay were the most frequent, detected in 50/82 (61 %) of the patients. The rest were large deletions detected in 14/82 (17 %), splice site mutations detected in 11/82 (13 %), missense mutations in four patients and mutations in the promoter sequence in three patients. Mutation mosaicism ranging from 10 to 30 % was detected by allele specific PCR in ten patients, 9 % (5/55) of patients with bilateral tumor and 33 % (5/15) of the patients with unilateral tumor. In three patients rare variants were detected as the only finding which was also detected in other healthy family members. Allele specific amplification of recurrent mutations raises in our cohort the identification rate from 82 to 91 % in the sporadic bilateral cases and from 13 to 19 % in the unilateral sporadic cases. Most mosaic cases could not be identified by Sanger sequencing and therefore screening for recurrent CpG transition mutations by allele specific amplification is of utmost importance. Molecular screening is important for the genetic counseling regarding the risk for tumor development and the relevance for prenatal diagnosis but in several families is accompanied by detecting rare variants that might be rare polymorphisms or low penetrant mutations.
Starting Page	471
Ending Page	480
Page Count	10
File Format	PDF
ISSN	13899600
Journal	Familial Cancer
Volume Number	14
Issue Number	3
e-ISSN	15737292
Language	English
Publisher	Springer Netherlands
Publisher Date	2015-03-10
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Retinoblastoma Mosaicism CpG transition mutations Cancer Research Human Genetics Epidemiology Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Genetics Cancer Research Genetics (clinical) Oncology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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