The next-gene sequencing procedure encompasses fragmenting RNA or DNA into different pieces, involving adapters, sequencing libraries, and reassembling all to produce a genomic sequence. In principle, the overall concept is similar to capillary electrophoresis.
The next-generation sequencing includes four basic steps –
- The library preparation
- The cluster generation
- The sequencing, and
- The alignment & data analysis
For BRCA1 and 2 Complete Gene sequencing, the testing for hereditary breast/ovarian cancer relies on laborious molecular tools. These use Sanger sequencing to scan for the mutations in BRCA1 & BRCA2 genes. Here’s everything to learn about BRCA1 & BRCA2.
What do you mean by BRCA1 & BRCA2?
At times referred to as tumour suppressor genes, breast cancer gene one or BRCA1 and breast cancer gene two or BRCA2 are genes producing proteins that repair the damaged DNA. The tumour suppressor genes are the gene type that produces a protein known as a tumour suppressor protein. It controls cell growth. Mutations in the tumour suppressor genes result in cancer – antioncogene.
Every individual comprises two copies of tumour suppressor genes. One of them is inherited from each parent. Individuals who inherit the harmful variant have higher risks of cancer, mostly ovarian or breast cancer. Individuals inheriting a harmful variant of tumour suppressor genes or BRCA 1 & BRCA 2 may develop cancer at a young age.
Every kid of parents carrying mutations in one of the genes has a greater chance of inheriting this mutation. The inherited mutations are known as germline mutations and are present from birth in the cells.
Suppose an individual inherits a harmful variant in the BRCA1 or BRCA2 from a parent. They might have also inherited a normal gene copy from another parent. However, this normal copy may change or be lost in certain cells in one’s body during the lifetime. This type of change is referred to as somatic alteration. Cells without any functional BRCA1 or BRCA2 proteins may grow out of control & become cancerous.
The Connection between Genes and Breast/Ovarian Cancer
A woman’s risk of breast or ovarian cancer is increased when she inherits a harmful variant in the BRCA1 or BRCA2. However, the level varies on the basis of mutation. According to the breast cancer reports, in 2020, 2.3 million women got diagnosed with breast cancer. By contrast, around 50 to 70 per cent of women inheriting the harmful BRCA1 variant and 40%–65% of women inheriting the BRCA2 variant can develop breast cancer by 70 to 80 years. So, the risk for women depends on a set of parameters, and some of them may not get characterized fully.
Women with cancer in their mammary glands have harmful BRCA1/BRCA2 variants. They may also have an increased chance of developing cancer in their contralateral breast in the forthcoming years. The contralateral breast cancer risk increases with time, depending on the involved gene. As per ovarian cancer reports, 1.2% of women may develop ovarian cancer during different stages of their life.
What to Expect from BRCA Sequencing and Testing?
The BRCA1 Next Generation Sequencing is a specified category of tests that look for genomic mutations in the tumour’s genes. Individuals who are prepared for the tests must expect a few things. The BRCA gene test is a blood test and can be practised only by a medical associate, technician, and nurse. The healthcare technician inserts one needle into the vein to draw a blood sample required for the testing. The sample is sent to the lab for analyzing the DNA.
In certain cases, other sample types are also collected for the DNA analysis that including saliva. People with a family history of cancer and interested in pursuing saliva DNA testing must discuss it with their medical practitioner. They can also consult a genetic counsellor to determine the most appropriate sample type for the testing. The result can either be positive or negative:
Positive:
It means that the individual has a mutation in one of their breast cancer genes, BRCA1/BRCA2, and a higher risk of developing ovarian or breast cancer. Note that a positive result does not always mean the person will develop cancer.
Uncertain or negative:
A negative result means no BRCA gene mutation has been discovered. But assessing the risk can still be difficult. The result is considered the “true negative” only when it finds the woman doesn’t carry a BRCA mutation identified in their relative.
As of now, researchers continue to study gene mutations that increase the risks of cancer. Also, there’s been a development in the practices of Next Generation Sequencing in India too.
