March 2023

Hereditary Breast and Ovarian Cancer (HBOC) is a genetic condition caused by mutations in the BRCA1 and BRCA2 genes. These genes are responsible for producing proteins that suppress tumour growth, and mutations in these genes can significantly increase a person’s risk of developing breast and ovarian cancer. The importance of HBOC genetic testing lies in its ability to identify individuals who carry a mutation in either the BRCA1 or BRCA2 genes. Early detection of these mutations allows for more personalized screening and prevention strategies that can ultimately save lives. Evolution of HBOC Genetic Testing The first BRCA1 and BRCA2 mutations were identified in the mid-1990s, and since then, genetic testing for these mutations has evolved significantly. Early genetic tests for HBOC involved sequencing individual genes, which was time-consuming and costly. However, with advances in technology, it is now possible to test for multiple genes associated with hereditary cancer in a single test. In 2013, the U.S. Supreme Court ruled that patents on the BRCA1 and BRCA2 genes were invalid, allowing for increased competition and a decrease in the cost of genetic testing. Today, HBOC genetic testing is widely available and accessible worldwide and in some countries with insurance coverage. Importance of HBOC Genetic Testing Identifying individuals who carry a BRCA1 or BRCA2 mutation is crucial for several reasons. It allows for earlier and more frequent cancer screening. Individuals who carry a BRCA mutation have a significantly higher risk of developing breast and ovarian cancer, and early detection can lead to better outcomes. For example, women with a BRCA1 or BRCA2 mutation are recommended to start annual mammograms and breast MRIs at a younger age than the general population. In addition to the importance of HBOC genetic testing for individuals with a family history of breast and ovarian cancer, it’s also important to consider the population risk of developing these cancers. While individuals with a family history of breast and ovarian cancer are at higher risk of carrying a BRCA1 or BRCA2 mutation, it’s estimated that up to 90% of individuals with a BRCA mutation do not have a family history of these cancers. Therefore, it’s important for all individuals to be aware of their risk and consider genetic testing if they meet certain criteria. The population risk of carrying a BRCA mutation varies depending on several factors, including ethnicity. For example, it’s estimated that 1 in 40 individuals of Ashkenazi Jewish descent carry a BRCA mutation, compared to 1 in 500 individuals in the general population. Other factors that may increase an individual’s risk of carrying a BRCA mutation include a personal history of breast or ovarian cancer, early onset of breast cancer, and having multiple family members with breast or ovarian cancer. Identifying BRCA carriers allows for preventative measures such as prophylactic surgery. Women who carry a BRCA1 or BRCA2 mutation have a lifetime risk of up to 70% for developing breast cancer and up to 44% for developing ovarian cancer. Prophylactic surgery, such as a bilateral mastectomy or oophorectomy, can significantly reduce the risk of developing these cancers. Finally, identifying BRCA carriers can help inform family members of their own cancer risk. BRCA mutations are inherited in an autosomal dominant pattern, meaning that each child of a carrier has a 50% chance of inheriting the mutation. By identifying carriers, family members can make informed decisions about their own cancer screening and prevention strategies. Conclusion Overall, HBOC genetic testing plays a vital role in identifying individuals who carry a BRCA1 or BRCA2 mutation, which can inform personalized cancer screening and prevention strategies. With the widespread availability and affordability of genetic testing, individuals with a family history of breast and ovarian cancer should consider testing and speak with their healthcare provider about their risk and management options. By identifying BRCA carriers, families can make informed decisions about their cancer risks and take steps to potentially reduce their risk of developing these cancers. References

Bioinformatics has become an essential tool in genetics and genomics, aiding in the identification of genetic variants that may be associated with the disease. With the advent of next-generation sequencing (NGS) technologies, bioinformatics approaches have become increasingly important in identifying and interpreting genetic variants accurately. In this article, we will discuss the bioinformatics approaches and tools used for variant reporting and their significance in identifying clinically relevant genetic variants. Variant Calling Variant calling is the process of identifying genetic variants from NGS data. It involves comparing the sequence reads obtained from a patient’s DNA to a reference genome and identifying differences, such as single nucleotide polymorphisms (SNPs), insertions, and deletions. Several variant calling algorithms are available, each with its strengths and weaknesses. Some popular variant calling algorithms include GATK, FreeBayes, and DeepVariant. These algorithms use statistical models and/or Artificial Intelligence to identify variants based on the quality of the sequence reads, depth of coverage, and other factors. Functional Annotation Once genetic variants are identified, the next step is to determine their potential impact on human health. Functional annotation involves annotating genetic variants with information on their location, functional significance, and potential impact on human health. Several databases, such as dbSNP, ClinVar, and ExAC, provide information on genetic variants and their potential impact on human health. Bioinformatics tools such as ANNOVAR and VEP can be used to annotate genetic variants with information from these databases and predict their functional significance. Pathogenicity Prediction Pathogenicity prediction involves predicting the likelihood that a genetic variant will cause disease. Several bioinformatics tools, such as SIFT, PolyPhen-2, and CADD, use various algorithms to predict the pathogenicity of genetic variants based on factors such as protein structure, conservation, and biochemical properties. Integration of Clinical and Genomic Data The final step in variant reporting is to integrate clinical and genomic data to identify clinically relevant genetic variants. This involves comparing genetic variants with information on the patient’s clinical history, family history, and other relevant factors to determine their potential clinical significance. Bioinformatics approaches, such as the use of clinical decision support systems (CDSS), can aid in this process by integrating genomic data with clinical information to provide personalized recommendations for patient care. Conclusion Bioinformatics approaches play a crucial role in variant reporting by providing effective solutions for identifying and interpreting genetic variants. With further advancements in bioinformatics and genomics, we can expect to see significant improvements in patient care and disease prevention in the years to come. Overall, bioinformatics tools have revolutionized the field of genetics and genomics, providing researchers and clinicians with valuable insights into the genetic basis of human health and disease. By leveraging these tools, we can improve our understanding of the genetic factors that contribute to disease and ultimately improve patient outcomes. Our GeneAssure Clinical Genomics Suite is simple, fast and repeatable variant analysis software for gene panels, exomes, and whole genomes. GeneAssure automates the NGS workflow from FASTQ to Reports. To know more about GeneAssure, reach out to us at contact@genespectrum.in