Abstract 3118
Background
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.
Methods
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.
Results
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
Mutations | Carrier (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.83del | P ♂ | U - |
c.861G>C | P ♀ | U - |
c.939G>A | P ♂ Grandfather Uncle | U - - U |
c.380 + 1G-A; с.1695 + 5G-T; c.1696-2A-G | P ♂ | B U |
Conclusions
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.
Funding
The state assignment of Ministry of Science and Higher Education of the Russian Federation.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3839 - Fenofibrate impairs pro-tumorigenic potential of cancer stem cell-like cells within drug-resistant prostate cancer cell populations.
Presenter: Tomasz Wróbel
Session: Poster Display session 3
Resources:
Abstract
3842 - Effect of docetaxel-resistance on the reactivity of prostate cancer cells to metformin
Presenter: Jessica Catapano
Session: Poster Display session 3
Resources:
Abstract
5198 - Cell plasticity and taxanes resistance in metastatic prostate cancer: ESRP1 as a predictive biomarker of taxane response
Presenter: Natalia Jimenez
Session: Poster Display session 3
Resources:
Abstract
2981 - Effect of Selumetinib plus AZD8186 treatment on Cabazitaxel sensitivity in docetaxel-acquired resistant metastatic prostate cancer cell lines
Presenter: Vicenc Ruiz de Porras
Session: Poster Display session 3
Resources:
Abstract
2779 - Anti-tumor activity of cediranib, a pan-inhibitor of vascular endothelial growth factor receptors, in pancreatic ductal adenocarcinoma cells
Presenter: Majid Momeny
Session: Poster Display session 3
Resources:
Abstract
1782 - The molecular mechanisms of EpCAM in regulating tumor progression and development of anti-EpCAM antibodies for colon cancer diagnosis and therapy
Presenter: Han-chung Wu
Session: Poster Display session 3
Resources:
Abstract
1322 - Detection of microRNAs as biomarker for anti-EGFR antibody resistance in colon cancer patients
Presenter: Jens Hahne
Session: Poster Display session 3
Resources:
Abstract
1579 - Serum exosomal microRNA-199b-5p as a novel circulating biomarker to predict response of preoperative chemoradiotherapy for locally advanced rectal cancer
Presenter: Dong Won Baek
Session: Poster Display session 3
Resources:
Abstract
1761 - Live biobank of patient-derived organoids from Thai colorectal cancer patients enables clinical outcome prediction
Presenter: Pariyada Tanjak
Session: Poster Display session 3
Resources:
Abstract
3542 - The biological implications of PDCD6 dysregulation in colorectal cancer
Presenter: Romina Briffa
Session: Poster Display session 3
Resources:
Abstract