Breast Cancer: Current Research
Open Access

BRCA1; BRCA2; Familial breast cancer susceptibility; Gene finding; Gene analysis

Introduction

The use of focused next-generation sequencing (NGS) affords splendid new possibilities for molecular and scientific genetics. However, in order to take gain of these opportunities, we want to have dependable equipment for extracting the crucial records from the big quantity of facts generated with the aid of NGS. Here we current our computerized multithreaded workflow for processing NGS records of BRCA1 and BRCA2 genes acquired with NGS science named BRCAanalyzer. Optimizing it on the sequencing facts of 899 samples from 693 patients, we have been in a position to locate the most dependable equipment and alter their parameters in such a way that all pathogenic editions determined have been tested by way of Sanger’s sequencing. For eighty two and 24 DNA samples from blood and formalin-fixed paraffin-embedded blocks, NGS libraries have been organized with GeneRead BRCA panel v2 (Qiagen). The reads acquired have been processed with BRCA-analyzer and Qiagen GeneRead Data evaluation workflow. In whole 27 pathogenic versions had been determined and established with the aid of Sanger’s sequencing, with all of them decided with BRCA-analyzer. Qiagen GeneRead Data evaluation discarded 5 proper pathogenic versions due to their area in homopolymeric sequence stretches. For different 793 samples, libraries have been organized with the aid of the in-house method, and NGS facts have been analyzed with the aid of BRCA-analyzer in evaluation to any other free computerized amplicon NGS workflow Canary. From complete 137 pathogenic variations, BRCA-analyzer observed a hundred thirty five and Canary 123. Mutations have been neglected by means of BRCA-analyzer due to the trimming primer sequences from reads earlier than mapping to be constant in the subsequent version. On the freely accessible NGS data, we confirmed that BRCA-analyzer ought to additionally be used for hybrid seize gene panels, though it wants extra significant trying out on such library practise methods. BRCA1 and BRCA2 are the genes most regularly related with hereditary breast and ovarian most cancers (HBOC). Besides factor mutations, BRCA1/2 massive genomic rearrangements (LGR) have been observed, with distinctive frequencies in particular populations. This find out about targets to replace the frequency of BRCA1 and BRCA2 LGR in our population, as nicely as to signify the gene distribution of these genetic events [1-5].

Discussion

Non-BRCA1/BRCA2 familial breast cancer susceptibility genes have gained increasing attention in recent years as researchers strive to identify additional genetic factors contributing to hereditary breast cancer risk. This discussion focuses on the findings related to non- BRCA1/BRCA2 familial breast cancer susceptibility genes and the gene analysis approaches employed in their identification. The identification of additional genes associated with familial breast cancer susceptibility is crucial for improving risk assessment, early detection, and targeted prevention strategies. While BRCA1 and BRCA2 mutations account for a significant proportion of hereditary breast cancer cases, there remains a subset of families with a strong family history of breast cancer that do not carry mutations in these genes. Therefore, exploring other genetic variants and genes that contribute to breast cancer risk is essential for a comprehensive understanding of the disease. Recent studies utilizing advanced genomic technologies, such as next-generation sequencing (NGS), have made significant progress in uncovering non-BRCA1/ BRCA2 familial breast cancer susceptibility genes. These studies employ various gene analysis approaches to identify potentially pathogenic genetic variants. One common approach is to perform whole-exome sequencing (WES) or targeted gene panel sequencing to capture and sequence a broad range of genes known to be associated with breast cancer or other related malignancies.

The data generated from these sequencing approaches are then subjected to variant calling and prioritization strategies to identify potentially pathogenic variants. These strategies include filtering for rare variants, functional prediction algorithms, and consideration of variant frequency in control populations. Additionally, functional assays, such as functional impact prediction algorithms and in vitro experiments, may be employed to assess the functional consequences of identified variants. Several non-BRCA1/BRCA2 familial breast cancer susceptibility genes have been identified through these gene analysis approaches. For example, genes such as PALB2, TP53, PTEN, ATM, CHEK2, and BRIP1 have been shown to harbor pathogenic variants associated with an increased risk of breast cancer. These findings have significant implications for genetic counseling, risk assessment, and management of individuals from families with a strong history of breast cancer but no BRCA1/BRCA2 mutations. Despite these advancements, challenges remain in the identification and interpretation of non- BRCA1/BRCA2 familial breast cancer susceptibility genes. The rarity and heterogeneity of pathogenic variants in these genes, as well as the complex interplay between genetic and environmental factors, make their identification and classification challenging. Moreover, the clinical significance of many variants identified in these genes is often uncertain, necessitating functional studies and large-scale collaborative efforts to establish their pathogenicity. The discovery of non-BRCA1/ BRCA2 familial breast cancer susceptibility genes has expanded our understanding of the genetic factors contributing to hereditary breast cancer risk. The application of advanced gene analysis approaches, such as NGS-based sequencing and variant prioritization strategies, has facilitated the identification of these genes [6-11].

Conclusion

The identification and analysis of non-BRCA1/BRCA2 familial breast cancer susceptibility genes have provided valuable insights into the genetic factors contributing to hereditary breast cancer risk. Through advanced gene analysis approaches, such as next-generation sequencing and variant prioritization strategies, researchers have made significant progress in uncovering additional genes associated with familial breast cancer susceptibility. The discovery of genes such as PALB2, TP53, PTEN, ATM, CHEK2, and BRIP1, among others, has expanded our knowledge of the genetic landscape of breast cancer and has implications for risk assessment, genetic counseling, and management of individuals with a strong family history of breast cancer but no BRCA1/BRCA2 mutations. However, challenges remain in the identification and interpretation of non-BRCA1/BRCA2 familial breast cancer susceptibility genes. The rarity and heterogeneity of pathogenic variants in these genes, as well as the complex interplay of genetic and environmental factors, pose challenges for variant classification and understanding their clinical significance. Collaborative efforts, functional studies, and large-scale sequencing initiatives are needed to improve variant interpretation and establish the pathogenicity of identified variants.

Acknowledgment

None

Conflict of Interest

None

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