Abstract 4066
Background
Breast cancer (BC) represents the most common malignancy and has the highest mortality among women, both in the world and in Kazakhstan. Approximately 20-30% of cases of hereditary breast cancer are caused by presence of BRCA1 and BRCA2 genes defects. Also, there are additional genes which can increase the risk of BC and they are still under study.The aim of this study was to identify new, detectable and objective markers of key cancer genes by next-generation sequencing (NGS) in BC patients.
Methods
The study included 194 unrelated patients (the av/age 34.25 ± 4.56) with BC. Genomic DNA was obtained from peripheral blood,next-generation sequencing was performed using TruSightCancer Kit on the MiSeq platform,studio Variant was used to annotate genetic variants.
Results
In total, 61 pathogenic variants (all in heterozygous state) were found in 56 (28.9%) patients,the vast majority of variants located in BRCA1 (n = 19/56; 33.9%), 15 in BRCA2 (26.8%). The frequency of pathogenic variants in genes TP53 (8.9%), PALB2 (5.4%), MSH6 (5.4%), CHEK2 (3.6%), SDHB (3.6%), and WRN (3.6%) were higher than those genes APC, ATM, FANCA, FANCM, MSH2, NBN, NF1, PMS1, PMS2, and XPA which include only one deleterious variants. The analysis of mutation type has revealed 28 frameshift mutations, 15 stop-gain mutations, 8 missense mutations, 8 splice site variants, 1 start lost variant, and 1 synonymous variant. In total, 43 mutations were unique, 15 of them represented novel variants. Those new mutations have not been previously mentioned in the LOVD and ClinVar databases and have not been described in publications. Population frequency of all detected pathogenic mutations in 1000G, ESP6500 and ExAC databases were less than 1%. 73.8% of the mutations were available in the dbSNP database. The most common pathogenic variants were c.5329dupC and c.5341-2delA (c.5278-2delA) in BRCA1 gene, accounting for 10.7% (n = 6/56) and 8.9% of patients (n = 5/56), respectively.
Conclusions
NGS showed frequent and novel germline mutations in BRCA1/2, CHEK2, TP53 and PALB2. After the final statistical data processing, diagnostic and prevention tools for key genes will be developed and included in the National guidelines for cancer diseases.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Kazakh Institute of Oncology and Radiology Institute of General Genetics and Cytology.
Funding
The Ministry of Healthcare of the Republic of Kazakhstan.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2262 - Real world experience of Nivolumab therapy in Metastatic Renal Cancer patients: a 3 year multi-centre review
Presenter: Joanna Hack
Session: Poster Display session 3
Resources:
Abstract
4441 - “A pilot study of tremelimumab (treme) with or without cryoablation (cryo) in patients (pts) in metastatic renal cell carcinoma (mRCC).”
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
2613 - Lenvatinib (Len) alone or in combination with Everolimus (Eve) in heavily pretreated patients (pts) with metastatic renal cell carcinoma (mRCC) after immune checkpoint inhibitors (ICI) and VEGFR-targeted therapies: A single-institution experience
Presenter: Andrew Wiele
Session: Poster Display session 3
Resources:
Abstract
3249 - Weight loss is an underestimated adverse event with cabozantinib in patients with metastastic renal cell carcinoma (mRCC).
Presenter: Emeline Colomba
Session: Poster Display session 3
Resources:
Abstract
2405 - Impact of corticosteroids on nivolumab activity in metastatic clear cell renal cell carcinoma.
Presenter: Felix Lefort
Session: Poster Display session 3
Resources:
Abstract
4020 - Skeletal muscle loss as an adverse event during Cabozantinib treatment in patients with metastatic renal cell carcinoma
Presenter: Carolina Alves Costa Silva
Session: Poster Display session 3
Resources:
Abstract
2407 - Long term relative survival (RS) in patients with primary metastatic kidney cancer (primary mRCC): an analysis of 2,167 patients from the Austrian National Cancer Registry (ANCR).
Presenter: Monika Hackl
Session: Poster Display session 3
Resources:
Abstract
2470 - Advanced renal cell carcinoma: first results from the prospective research platform CARAT for patients with mRCC in Germany
Presenter: Peter Goebell
Session: Poster Display session 3
Resources:
Abstract
1533 - Are immune checkpoint inhibitors a valid option for papillary Renal Cell Carcinoma? Transcriptomic characterization of the immune infiltrate
Presenter: Manon De Vries-brilland
Session: Poster Display session 3
Resources:
Abstract
3367 - Treatment-Free Survival, With and Without Toxicity, as a Novel Outcome Applied to Immuno-Oncology Agents in Advanced Renal Cell Carcinoma
Presenter: Meredith Regan
Session: Poster Display session 3
Resources:
Abstract