HRR Referene Standard

In breast cancer (BC), the tumor suppressor network with BRCA1/2 as the core is mainly involved in the repair process of DNA doublestrands breaks (DSB) caused by various factors including ionizing radiation. Proteins constitute a functional complex that regulates homologous recombination repair (HRR). Mutations or SNPs of key factors in this network may cause the loss of DNA repair capabilities, cause genome instability, and lead to cancer.

At the same time, the latest NCCN guidelines also clarify the relationship between HRR and prostate cancer in prostate cancer, requiring that the acquisition of family history and genetic counseling for prostate cancer patients who have not undergone risk assessment at the first diagnosis and are at very low to moderate risk should be tested. Prerequisite steps: For patients with the above-mentioned risk levels who have a clear family history and known family members who carry germline disease-causing gene mutations, it is recommended to perform DNA damage repair related genes (especially BRCA2, BRCA1, ATM, PALB2, CHEK2, MLH1 , MSH2, MSH6, PMS2) germline mutation detection; for the above-mentioned risk level patients with unknown family history, it is necessary to comprehensively judge whether relevant testing is necessary after genetic consultation based on clinical characteristics. For high-risk, extremely high-risk, locally advanced, and metastatic prostate cancer patients, it is recommended to perform germline mutation detection of DNA repair genes (especially BRCA2, BRCA1, ATM, PALB2, CHEK2, MLH1, MSH2, MSH6, PMS2).

In addition, in other tumors, such as pancreatic cancer, ovarian cancer, bladder cancer, etc., especially ovarian cancer, DNA cross-linking agents (such as platinum drugs) and poly ADP-ribose polymerase inhibitors (Poly ADP-ribose Polymerase inhibitors, PARPi) In these tumors, when HRD caused by abnormal HRR occurs, the patient is definitely benefited.

Homologous Recombination Repair (HRR) is an important way to repair DNA double-strand damage. HRR is a complex signal pathway involving multiple steps, among which the key proteins are BRCA1 and BRCA2. According to ARIEL3’s report, the pathways mainly involve BRCA1, BRCA2, ATM, ATR, BARD1, BLM, BRIP1, CDK12, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCF, FANCI, FANCL, FANCM, MRE11A, NBN, PALB2, PPP2R2A, RAD50, RAD51B, RAD51C, RAD51D, RAD52, RAD54L and RPA1 are 28 genes. Many mutations of these genes can cause abnormal DNA repair, which is closely related to the occurrence, diagnosis and treatment of tumors.

This standard product simulates clinical samples, contains all human genomes, and has a similar background to clinical samples (such as tumor chromosomal abnormalities). It contains 28 HRR-related genes, each of which has mutations, and the mutation types are diverse (synonymous, missense) , Deletion, insertion, splicing variation, copy number variation, etc.), clinical annotations are also diverse, necessarily including Benign, Likely Benign, Uncertain Significance, Likely Pathogenic, Pathogenic types, and the mutation frequency is near LOD (such as 1%, 2%, 5%), there are intermediate frequency (10%-50%), and high frequency (such as 100%). It has passed 1000x WES calibration, 3500x panel calibration, and DdPCR partial site calibration. The indicators are analyzed and used as reference data for the performance evaluation and daily quality control of HRR testing methods and testing kits.

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