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
1984 - Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC)
Presenter: Gizem Kaval
Session: Poster Display session 3
Resources:
Abstract
4822 - Efficiacy of different nutritional intervention on nutritional status and quality of life for local advanced nasopharyngeal carcinoma patients: a prospective clinical trial
Presenter: Yuan-yuan Chen
Session: Poster Display session 3
Resources:
Abstract
2628 - Apatinib in treating patients with platinum-resistant or platinum-refractory recurrent or metastatic nasopharyngeal carcinoma
Presenter: Changjuan Tao
Session: Poster Display session 3
Resources:
Abstract
4887 - Impact of tumor site and adjuvant radiotherapy on survival of adenoid cystic carcinoma: a SEER database analysis
Presenter: Jason Tasoulas
Session: Poster Display session 3
Resources:
Abstract
2634 - Efficacy and safety of anlotinib for patients with recurrent and/or metastatic salivary gland carcinomas
Presenter: Wen Jiang
Session: Poster Display session 3
Resources:
Abstract
3568 - ACCURACY a phase (P) 2 trial of AL101, a pan-Notch inhibitor, in recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) patients (pts) with Notch activating mutations (Notch act mut): preliminary safety and efficacy data.
Presenter: Renata Ferrarotto
Session: Poster Display session 3
Resources:
Abstract
683 - Pathologic Staging Changes in Oral Cavity Squamous Cell Carcinoma—Stage Migration and Implications for Adjuvant Treatment
Presenter: Zain Husain
Session: Poster Display session 3
Resources:
Abstract
563 - Expression of immune response biomarkers in head and neck squamous cell carcinoma (HNSCC) in irradiated area
Presenter: Carole Pflumio
Session: Poster Display session 3
Resources:
Abstract
4030 - HLA-Ligandome analysis reveals target antigens of oropharyngeal squamous cell carcinoma
Presenter: Simon Laban
Session: Poster Display session 3
Resources:
Abstract
2979 - Topographical distribution of sentinel lymph nodes in early tongue squamous cell carcinomas
Presenter: Hiroyuki Goda
Session: Poster Display session 3
Resources:
Abstract