BackgroundGermline mutations BRCA1 and BRCA2 contribute almost equally in the causation of breast cancer (BC). The type of mutations in the Indian population that cause this condition is largely unknown.PurposeIn this cohort, 79 randomized BC patients were screened for various types of BRCA1 and BRCA2 mutations including frameshift, nonsense, missense, in-frame and splice site types.Materials and methodsThe purified extracted DNA of each referral patient was subjected to Sanger gene sequencing using Codon Code Analyzer and Mutation Surveyor and next-generation sequencing (NGS) methods with Ion torrent software, after appropriate care.ResultsThe data revealed that 35 cases were positive for BRCA1 or BRCA2 (35/79: 44.3%). BRCA2 mutations were higher (52.4%) than BRCA1 mutations (47.6%). Five novel mutations detected in this study were p.pro163 frameshift, p.asn997 frameshift, p.ser148 frameshift and two splice site single-nucleotide polymorphisms (SNPs). Additionally, four nonsense and one in-frame deletion were identified, which all seemed to be pathogenic. Polymorphic SNPs contributed the highest percentage of mutations (72/82: 87.8%) and contributed to pathogenic, likely pathogenic, likely benign, benign and variant of unknown significance (VUS). Young age groups (20–60 years) had a high frequency of germline mutations (62/82;75.6%) in the Indian population.ConclusionThis study suggested that polymorphic SNPs contributed a high percentage of mutations along with five novel types. Younger age groups are prone to having BC with a higher mutational rate. Furthermore, the SNPs detected in exons 10, 11 and 16 of BRCA1 and BRCA2 were higher than those in other exons 2, 3 and 9 polymorphic sites in two germline genes. These may be contributory for BC although missense types are known to be susceptible for cancer depending on the type of amino acid replaced in the protein and associated with pathologic events. Accordingly, appropriate counseling and treatment may be suggested.

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Background and Objectives: Human cell nucleus has, the genome consisting of euchromatin and heterochromatin. The euchromatin has gene-rich and actively functional. The heterochromatin has two components namely constitutive and facultative, where the former is highly polymorphic. It is related to numerous diseases like cancer and infertility which is now well known, though it was earlier thought to be inactive; hence the implication of these polymorphic variants of chromosomes is reviewed with respect to acrocentric and non- acrocentric types. Methodologies: The polymorphic variants can be detected by C, G, Q and R banding techniques. We usually follow G band preparation of karyotypes following World Health Organisation (WHO) manuals and their role in cancer and reproduction is reviewed. Review and Conclusion: It is emphasized that most of the p and q arms of 1, 9, 16, D and G groups and X, Y chromosomes exhibited polymorphism which are related to cancerous and infertile conditions in both sexes. Data on few non-acrocentric chromosomes like 2, 4, 8, 10, 12, 18, 19 and 20 are not available. Our review however indicated that the evaluation of specific heteromorphic variants needs to be detected using specific probes for confirmation of anomaly to assist affected cases, though earlier data indicated ambiguous information with few cases analyzed regarding assisted reproductive technologies and malignancy condition. This appraisal thus would play a key role in human chromosomal heteromorphic abnormalities and recommend genetic tests and counseling ultimately made available to the affected cases.

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