HRD testing is imperative, how to standardize?Expert consensus is coming!

*For medical professionals for reading reference

Interpret "Homoton Reorganization Repair defects Clinical Detection and Application Expert Consensus (2021 Edition)"

For pathologists, the diagnosis of tumors is crucial.

In recent years, tumor diagnosis and treatment requirements have become more and more accurate and individualized, and genetic testing has become an important reference indicator for formulating treatment plans.

Gene testing is often performed in third -party testing companies, but its standardized and interpretation of consistency issues require focus on attention. Genetic testing has become a trend. Genetic testing in hospitals can improve its normative and accuracy, which is conducive to subsequent treatment of tumor patients. However, this is a challenge for pathologists.

"Medical Channel" interpreted the "Clinical Testing and Application Experts (2021 Edition)" of "Homoton Reorganization Repair defects (2021)" to introduce the requirements for pathological diagnosis of homologous reorganization repair defect detection.

1. Definition of homologous reorganization repair defects (HRD)

Homoton Reorganization Repair (HRR) is the preferred repair method of DNA dual -chain break (DSB). Himant -source restructuring repair defect (HRD), that is, the functional disorders of HRR (usually causing insertion/lack of nucleic acid sequences, abnormal copies, chromosomal cross -linking, etc.), which can be mutated by HRR -related gene embryo, body cell mutations, or apparent genetic genetic inheritance Delivery and other reasons are caused by various reasons that are currently playing an important role in tumors such as ovarian cancer, breast cancer, pancreatic duct cancer, and prostate cancer, and can give clinical corresponding drugs according to their test results. HRD will produce specific, quantifiable, stable genome changes, so we can establish an evaluation system based on genome -based feature analysis to predict the state and degree of tumor HRD, and give medication support.

2. Establish an HRD evaluation system

1. Specimen treatment

The preferred ballad embedded tissue (within 3 years) is guaranteed to be used enough tumor cells for detection. (Fresh tissue needs to evaluate the tumor cell content and provide patients with peripheral blood as a control sample, so it is not recommended to use fresh tissues.) At present Method of this detection method.

Gene test: NCCN guidelines are recommended for BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, Chek1, Chek2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L, and PPP2R2A. Change, insert/lack, amplification, etc.

Genome scar and mutation spectrum analysis: HRD genome scar detection can be scored by chip or NGS platform, but there is currently no related HRD clinical testing kit in my country, and foreign detection data cannot be used to develop domestic kits; mutations based on all genome -based mutations Spectrum analysis can obtain a complete mutation process of tumor cells, but its specificity is low, which is not practical for detecting HRD -related drugs.

HRD functional detection: HRD functional detection is usually the ability to evaluate RAD51 to form the nuclear focus required for functional homologous reorganization during DNA damage, and real -time feedback of the HRD state of tumor cells. However, it is difficult to evaluate the benefits of patients and cannot be applied clinically.

Note: At present, genomic scar detection is the most cost -effective detection technology and more practical value. However, there are currently only foreign commercial kits. Therefore, in actual application in China, you need to communicate in advance and report carefully.

2. Report specification

1) Basic information:

① The information of the subject, including name, gender, age, clinical diagnosis, pathological diagnosis, genetic testing history, family history, and clinical treatment history, etc.;

② Sample information, including sample types, pathological numbers, sample collection time, inspection institutions, inspection doctors, inspection date and report time, etc.;

③ Project profile, including detection methods, detection platforms, detection content, library construction and reference genome, data analysis process, software and versions, etc.

④ Sample quality conditions, such as tumor cell proportion.

2) Detection results:

① quality control results, including Q30, sequencing depth, coverage, etc.;

② BRCA1/2 mutant state, HRR -related gene mutation status, HRD score and results interpretation.

3) Annotation of test results:

① HRD assessment, including BRCA1/2 pathogenic variation, other genetic variations involving HRR signaling pathways, the HRD score and threshold judgment rules of genomic unstable, and the use of BRCA1/2 harmful variation and HRD scores for HRD status judgment the rule of.

② Results interpretation, including whether there is a clear threshold description. Different cancer species and different PARP inhibitors should list the clinical trial evidence support of different thresholds and medication.

③ Based on the BRCA gene mutation positive patients involving the hereditary reminder of the embryo system, it is recommended that its direct relatives detect whether the mutation is carried.

4) Signature: Sign signed by the testing technicians and auditors. The final report should be subject to intermediate titles or master's degree or above, with a pathological professional background, qualified for training physicians or authorized signatures (senior titles or doctoral degree) for review Essence

5) Location description: According to information such as tumor type, type of samples, detection of Panel, and related clinical research results, the limitations of HRD clinical applications are explained.3. Summary and outlook

For tumors such as ovarian cancer, breast cancer, pancreatic duct cancer, prostate cancer, etc., HRD tests have been found in HRD.You can provide medication guidance for patients, and you can also give health advice to his close relatives.However, it is still important to note that it is still far from the actual clinical application (mainly in the lack of large -scale research, specifications and uniform material collection report models for Chinese people).It is believed that with the rapid development of genetic testing technology, HRD's precise evaluation will further improve the diagnosis and treatment of related tumors and benefit more patients.

First of this article: The pathological channel of the medical community

Author of this article: Zhao Meng

Audit expert: Professor Dong Lin, Cancer Hospital of the Chinese Academy of Medical Sciences

Editor in charge: Sweet

- END -