Identify-the-most-common-germline-ERBB-family-SNPs-in-HER-2-positive-Breast-Cancer-patients-via-high

Breast cancer (BC) is the most common malignancy in women with over 25% of all cancers being diagnosed as BC in 2018. HER2-positive BC accounts for around 20% of all human BCs and HER2 overexpression is associated with poor prognosis and an aggressive phenotype. Trastuzumab is a monoclonal antibody targeted to HER2, has well established efficacy in the treatment of HER2-positive BC. However, a significant proportion of patients with the disease have tumors that initially do not respond or that acquire resistance to trastuzumab after an initial period of response . ERBB-family genes which encode the HER family of proteins EGFR, HER2, HER3 and HER4 are commonly studied in HER2-positive BC, and some studies have identified the role of HER2 SNPs in response to trastuzumab .Here we want to identify the most common germline ERBB-family SNPs in HER-2 positive BC patients by via high depth NGS Aim : Here we want to identify the most common germline ERBB-family SNPs in HER-2 positive BC patients by via high depth NGS.

Methods (Sequencing analysis) :

1-Download two samples whole exome sequencing of Irish HER2+ breast cancer patients from SRA (paired end) Library: Name: SOL6717_R1 (The custom library designed comprised of 132 regions) 2-Check QC and Trimming in case of bad quality 3-Reads will be aligned with BWA. 4-Duplicate reads will be marked by Picard tools 5-local realignment and base recalibration will be conducted with GATK 6-Joint variant calling using HaplotypeCaller 7-Split SNPs and indels 8-Assess the different filters in both known and novel to decide the threshould for the filteration in each filter. 9-SNP Variant filteration 10-separate the passed SNPs in a vcf file