Publications
Clinica Chimica ActaMay 2024 |
558
118271
DOI:
10.1016/j.cca.2024.118271

Use of next generation sequencing for detection of hereditary cancer genes: A shared experience from the UAE national reference laboratory

Yasaei, H.; Maden, N.; Singh, H.; Flores, M.A.; Jaroudi, S.; Al Bisari, S.
Product Used
NGS
Abstract
Background-Aim Hereditary cancer syndromes are a heterogenous group of genetic diseases usually associated inheritance of pathogenic variant which increases risk of individuals to tumor development. Examples include Hereditary Breast and Ovarian Cancer, Fanconi Anemia, Blooms syndrome and Ataxia-telangiectasia to name a few. Most of these syndromes involve biallelic inactivation of genes involved in DNA repair and often characterized by severe immune deficiency. Collectively, at least 2 % of healthy people may carry pathogenic variant associated with highly increased risk of a certain cancer. Methods Illumina Miseq or NextSeq2000 were used to sequence all samples using 47 gene-panel (Twist Biosciences). Fastq files were then generated and aligned with hg19 reference genome using in-house GATK-based bioinformatics pipeline. Variant annotation and calling were done using various online databases and final classification of variants followed the ACMG guidelines. Pathogenic and likely pathogenic variant and variant of uncertain significance leaning likely pathogenic was reported Results A total of 171 patients underwent hereditary gene panel NGS testing. Median age of participants were 44 [range: 18-71], with 17.5 % (n = 30) reported to have P/LP variants. Arab nationals were 53 % of the total participant (n = 92) with majority being female (n = 158; 92 %). With 37.5 % of patients (n = 64) reported with variant of uncertain significance. Breast cancer or family history of breast cancer was the most common clinical indication (n = 120), with 79 patients with confirmed positive family history of cancer. In another cohort, we tested 158 confirmed majority of breast cancer patients for HER2neu amplification using FISH. Of the total cases of 158, 28 % (n = 44) was reported as group-1 positive. Conclusions Routine genetic testing of presumably healthy individuals for genes associated with hereditary cancer syndrome should allow for identification of at-risk individuals whereby genetic counselling and regular monitoring of such individuals with pathogenic or likely pathogenic variant with the health provider is recommended. Furthermore, identification of variant of uncertain significance can help to further perform functional study to ascertain the molecular impact of such variants on tumorigeneses.
Product Used
NGS

Related Publications