Abstract 3651
Background
Retinoblastoma (RB) is an embryonic malignant tumor of retina caused by inactivation of both alleles of the RB1 tumor suppressor gene. Identifying low-level mosaic mutations in RB1 gene in blood samples is challenging. Mosaic mutations arise in early embryogenesis and require high-resolution techniques for detection. In approximately 10% of families, the initial RB1 mutation is mosaic. The ability to identify RB1 mosaicism is important for genetic counseling because mosaicism increases the risk for developing RB in the other eye, second cancers and transmitting the mutation to progeny.
Methods
Using NGS we have evaluated the spectrum and frequency of RB1 mutations mosaicism in peripheral blood of 120 patients with sporadic RB (82 unilateral and 38 bilateral).
Results
In 5,8% (7/120) of patients a low-level mosaic mutation was found. The spectrum of identified mosaic RB1 mutations, the degree of mosaicism and clinical characteristics are shown in the table. Additionally, we analyzed the Sanger sequencing data from 72 blood samples from patients with sporadic RB (48 unilateral and 24 bilateral), performed earlier in our laboratory, and have not identified mosaic cases.Table: 404P
The spectrum of identified mosaic RB1 mutations
| Sample | Form (uni/bi-l ateral) | Age of onset | Mosaic mutation | Degree of mosaicism,% | Mutation in relatives |
|---|---|---|---|---|---|
| RB1 | Uni- | 6 mo | c.C1363T (14ex) | C:80, T:20 | Negative |
| RB2 | Uni- | 1yr 8 mo | c.C1363T (14ex) | C:74, T:26 | Negative |
| RB3 | Bi- | 3 weeks | c.2326delC (23ex) | wt:80, del:20 | Negative |
| RB4 | Uni- | 3 yr | c.C958T (10ex) | C:80, T:20 | Negative |
| RB5 | Uni- | 3 mo | c.C751T (8ex) | C:84, T:16 | Negative |
| RB6 | Uni- | 1 yr 8 mo | c.1215 + 1G-A (12ex) | G:87, A:13 | Negative |
| RB7 | Uni- | 8 mo | c.C1735T (18ex) | C:79, T:21 | Negative |
| RB8 | No symptoms | No | c.887delT (9ex) | wt:85, del:15 | Positive bilateral daughter |
Conclusions
NGS is an efficient method for detecting low-level mosaic mutations in blood samples from RB patients. Clinically, RB1 mosaicism is variable, it can manifest as a bilateral or a unilateral form with early or late onset, or without disease, which make the diagnosis even more difficult.
Clinical trial identification
Legal entity responsible for the study
FASO Russia.
Funding
The research was carried out within the State assignment of FASO Russia.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2595 - Real-Life Utilization of Genomic testing for invasive Breast Cancer patients in Italy and France reduces Chemotherapy Recommendations
Presenter: Sandro Barni
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
2343 - Benefit of adjuvant chemotherapy in hormone receptor-positive, HER2-negative, invasive lobular carcinoma of the breast
Presenter: Alexandre De Nonneville
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
2990 - Baseline lymphocyte counts predict distant recurrence in early breast cancer
Presenter: Gun Min Kim
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
4532 - A propensity score analysis exploring the impact of the addition of adjuvant chemotherapy (aCT) to hormone therapy (aHT) in a multi-center series of resected luminal early stage pure Invasive Lobular Breast Carcinoma (ILC).
Presenter: Luisa Carbognin
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
2344 - Benefit of Adjuvant Systemic Therapies in HR+ HER2- pT1ab Node-Negative Breast Carcinomas
Presenter: Alexandre De Nonneville
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3525 - Anti-proliferative effect of oral metronomic vinorelbine in PAM50 Luminal/HER2-negative early breast cancer (SOLTI-1501 VENTANA): an open-label, randomized, three-arm, multicenter, window-of-opportunity study
Presenter: Aleix Prat
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3908 - Clinicopathologic significance of androgen receptor expression and discordant receptor status during progression in breast cancer
Presenter: Chan Heun Park
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
4075 - The outcomes of early breast cancers utilizing the Oncotype Dx Recurrence score (RS) instead of Clinico-pathological (CP) factors for prognostic risk assessment: A Single Institution Experience
Presenter: Adhar Alsayed
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
738 - Circulating tumor cells as a prognostic marker in non metastatic breast cancer patients.
Presenter: Summar Elmorshidy
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3151 - Molecular subtyping of breast cancer by dedicated breast PET
Presenter: Satoshi Sueoka
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract