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Poster Display session 3

3118 - A parent-of-origin effect of the RB1 mutations in retinoblastoma with low penetrance and variable expressivity


30 Sep 2019


Poster Display session 3


Tumour Site

Head and Neck Cancers


Ekaterina Alekseeva


Annals of Oncology (2019) 30 (suppl_5): v449-v474. 10.1093/annonc/mdz252


E.A. Alekseeva1, O.V. Babenko1, V.M. Kozlova2, T.L. Ushakova2, T.P. Kazubskaya2, S.V. Sahakyan3, A.S. Tanas1, D.V. Zaletaev4, V.V. Strelnikov1

Author affiliations

  • 1 Epigenetics, Federal State Budgetary Scientific Institution "Research Centre for Medical Genetics", 115478 - Moscow/RU
  • 2 Institute Of Pediatric Oncology And Hematology, Federal State Budgetary Institution «N.N. Blokhin National Medical Research Center of Oncology» оf the Ministry of Health of the Russian Federation, 115478 - Moscow/RU
  • 3 Clinical Centre, Federal State Budgetary Institution «Helmholtz Moscow Research Institute of Eye Diseases», 105062 - Moscow/RU
  • 4 Medical Genetics, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119991 - Moscow/RU


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Abstract 3118


Retinoblastoma (RB) is the most common pediatric intraocular neoplasm caused by the biallelic inactivation of the RB1 tumor suppressor gene. In 40% of cases, the development of RB is mediated by a germline mutation in one of the alleles of RB1. Patients with germline mutation develop bilateral tumor with penetrance of more than 90%. However, some families demonstrate cases of RB with low penetrance (unaffected carries) and variable expressivity (carries develop either bi- or uni- RB).

It is believed that the phenotypic manifestation of hereditary retinoblastoma depends on the functional type of the germinal mutation in the RB1. The molecular mechanisms underlying the variable phenotypic manifestation of the same mutation in different family members are currently explained by the parent-of-origin effect of RB1 mutation.


Using NGS of the RB1 we have analyzed DNA from blood of 331 unrelated patients with RB (226 patients with uni- RB and 105 with bi- RB). DNA samples of available family members were also examined for the presence of an identified mutation using Sanger sequencing.


We identified 11 germline mutations in the RB1 that led to the RB with low penetrance and/or variable expressivity in 12 families. Among the identified mutations:, 25.0% - are missense mutations, 58.3% - are splice mutations and 16.7% - are frame shift mutations. In 91,7% of cases, probands inherited the mutant allele from their fathers, who were either clinically healthy carriers (7 families) or had the uni-/bilateral form of RB (3 families).Table: 1170P

MutationsCarrier (Proband, P)Form (uni, U; bi-lateral, B; no symptoms, -)
c.1364G>C; c.1573G>A; c.1981C>T; с.607 + 1G-T (2 families); c.45_76del; с.83delP ♂U -
c.861G>CP ♀U -
c.939G>AP ♂ Grandfather UncleU - - U
c.380 + 1G-A; с.1695 + 5G-T; c.1696-2A-GP ♂B U


The identification of mutations in the RB1 leading to the development of RB with low penetrance and variable expressivity, is necessary for adequate treatment and competent determination of the risk of developing the disease in other family members.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

State assignment of Ministry of Science and Higher Education of the Russian Federation.


The state assignment of Ministry of Science and Higher Education of the Russian Federation.


All authors have declared no conflicts of interest.

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