As a company that provides enterprise nucleic acid diagnostic standard products, Cobioer has been deeply involved in this field for many years. It has cooperated with 90% of enterprises in this field in the country, and has successfully supported the development and approval of kits of many enterprises. extremely experienced. According to our market research and understanding of customer needs, we divide our product line into multiple modules, mainly single-point mutation, fusion and CNV products that support PCR, and small panels and large panels that support NGS. , Including TMB and MSI) products, FFPE block products that support IHC and FISH, ddPCR detection kit products that support standard product calibration, etc.
In the next few issues, we will follow the NCCN guidelines for unused tumors and share our views on the selection of corporate reference products.
Prostate cancer refers to an epithelial malignant tumor that occurs in the prostate. The 2004 WHO "Pathology and Genetics of Tumors of Urinary System and Male Reproductive Organs" included adenocarcinoma (acinar adenocarcinoma), ductal adenocarcinoma, urothelial carcinoma, squamous cell carcinoma, and adenosquamous carcinoma in the pathological types of prostate cancer. . Among them, prostate adenocarcinoma accounts for more than 95%. Therefore, usually what we call prostate cancer refers to prostate adenocarcinoma. In 2012, the incidence of prostate cancer in my country's tumor registration areas was 9.92 per 100,000, ranking sixth in the incidence of male malignant tumors. The age of onset is at a low level before 55 years of age, and gradually increases after 55 years of age. The incidence rate increases with age, and the peak age is 70 to 80 years. The age of onset of familial prostate cancer is earlier, and 43% of patients are younger than 55 years old.
For the diagnosis of prostate cancer, the most important thing written into NCCN and expert consensus is the germline and systemic mutations of HRR (homologous recombination repair) genes, in addition to microsatellite instability (MSI) and DNA mismatch repair Defect (DNA mismatch repair deficiency, dMMR) detection, there are some unspecified genes.
HRR related genes
For the newly diagnosed prostate cancer patients who have not undergone risk assessment and are extremely low-risk to medium-risk, the acquisition of their family history and genetic counseling are necessary steps before the test: For those who have a clear family history and are known to carry germline pathogenic genes For patients with mutations at the above risk levels, it is recommended to perform germline mutation detection of DNA damage repair related genes (especially BRCA2, BRCA1, ATM, PALB2, CHEK2, MLH1, MSH2, MSH6, PMS2); for patients with the above risk levels with unknown family history , It is necessary to comprehensively judge whether it is necessary to carry out relevant tests after genetic counseling 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).
For HRR-related genes, Cobioer Biosciences has launched a variety of related standard products:
Mismatch repair gene
A retrospective study found that the clinical and pathological characteristics of patients with mismatch repair gene mutant prostate cancer are more aggressive. Foreign studies have reported that the proportion of dMMR and MSI-H patients in prostate cancer patients is 2%~5%. Another study reported that about 3% of prostate cancer patients carry MSH2 (2%), MLH1 (1%), MSH6 (1%) and PMS2 (<1%) gene somatic mutations. Patients with these gene mutations often have The highest overall number of gene mutations. Among the 316 cases of prostate cancer in China, the proportion of patients carrying germline pathogenic variants of MSH6 and MSH2 genes was 0.63%, and no patients carrying germline pathogenic variants of MLH1 and PMS2 genes were found.
The "NCCN Guidelines" recommend MSI-H and dMMR testing for patients with local progression, metastasis, and mCRPC. If diagnosed with MSI-H or dMMR, patients with mCRPC can consider pembrolizumab treatment (category 2B) at a specific stage of treatment, while genetics are required Consultation and consideration of Lynch syndrome (Lynch syndrome) related gene testing, further MMR gene germline mutation testing can clarify its genetic changes.
Cobioer Gene has launched a number of MSI test standards:
HOXB13 gene: The "Philadelphia Consensus" proposes that the HOXB13 gene related to hereditary prostate cancer needs to be tested (consensus rate 95%), the main mutations are G84E and G135E.
RB1 gene: A number of recent studies have found that RB1 gene mutations or deletions have important prognostic value for mCRPC patients. In mCRPC, RB1 gene mutations or deletions are associated with worse survival and shorter abiraterone or enzalutamide. The treatment time is related.
AR gene: AR gene amplification/ligand domain variation (such as AR-V7) is also associated with decreased sensitivity of prostate cancer to abiraterone and enzalutamide.
TP53 gene: TP53 mutations are also associated with decreased sensitivity to abiraterone and enzalutamide in prostate cancer.
FOXA1 gene: FOXA1 is an important gene related to the AR receptor pathway. The high expression of FOXA1 is related to the poor prognosis of prostate cancer. A recent study of 208 patients with limited-stage prostate cancer found that 41% of Chinese patients carry the FOXA1 mutation, which is much higher than the proportion of patients in western developed countries. And most of the FOXA1 mutations in Chinese patients are hotspot mutations, which may promote the occurrence and development of prostate cancer by regulating the AR pathway.
These genetic-related standard products are all under development. Welcome to inquire...