1.What is MMR gene?
MMR is the abbreviation of English mismatch repair, mismatch repair is mismatch repair. MMR gene is a conserved gene in the evolutionary process of organisms and belongs to the housekeeping gene, which can repair DNA base mismatches, facilitate high fidelity of DNA replication, help maintain the stability of the genome and reduce spontaneous mutations, etc.
2.What is microsatellite?
Microsatellite sequences, also known as simple repetitive sequences, are short and repetitive DNA sequences, generally consisting of 1-6 nucleotides, which can be repeated 20-60 times or even more. Most of them are dinucleotide or trinucleotide repeat units, and the copy number varies thus determining the length of microsatellite sequences.
3.What is microsatellite instability (MSI)?
Microsatellite instability (MSI) refers to the deletion of mismatch repair (MMR) genes due to DNA methylation or gene mutation, resulting in changes in the length of microsatellite repeat sequences. The MSI test can be used to diagnose Lynch syndrome.
4.Why does uncontrolled MMR system cause tumor?
MMR system deregulation can lead to microsatellite sequence instability (MSI) or mutations in genes encoding functional proteins, which can further lead to MMR protein expression deficiency, thus altering normal cellular function and causing tumors.
5.What are the members in MMR family?
There are hMLH-1, hMSH-2, hPMS-1 and hPMS-2 proteins, among which hMLH-1 and hMSH-2 proteins are the main members of the MMR family and play an important role in the evolution of colorectal cancer.
6.What is the relationship between sporadic colorectal cancer and MMR?
Some sporadic colorectal carcinoma (SCC) has hMLH-1 and hMSH-2 protein deletion, mainly due to hMLH-1 gene promoter hypermethylation resulting in transcriptional and translational silencing of gene expression. Mismatch repair gene hMLH1 and hMSH2 mutations are closely related to the occurrence and development of colorectal cancer.
7.What is the prognosis of MMR-deficient patients?
Compared with patients with normal DNA repair function, tumors of MMR-deficient patients have lower recurrence rate, longer remission period, lower metastasis and higher survival rate. prognosis of MMR-deficient patients is relatively good.
8.When do I need MMR gene testing?
Stage II colorectal cancer, patients with high-risk factors and need adjuvant chemotherapy. If available, it is recommended to test tissue specimens for MMR or MSI. If dMMR or MSI-H, single-agent adjuvant chemotherapy with fluorouracil-based drugs is not recommended. Please note that combination chemotherapy regimens such as 5-FU/LV/oxaliplatin, CapeOx, etc. may also be affected.
9.How many patients with colon cancer have MMR functional defects?
Approximately 15% of colon cancer patients have defective mismatch repair (MMR) function.
10.Can MMR functional status affect the therapeutic effect of 5-FU?
MMR functional status affects the therapeutic effect of 5-FU. stage II colon cancer patients with MMR defects have a significant effect on the therapeutic effect of 5-FU and are suitable for 5-FU treatment. stage III-IV colon cancer patients with MMR status seem to have no difference in the therapeutic response to 5-FU, and 5-FU is effective in suppressing tumor recurrence whether there is a defect in MMR function or not.
11. Is it valuable to detect hMLH-1 and hMSH-2 proteins?
The results of hMLH-1 and hMSH-2 protein expression changes can be a good predictor of MMR function defects and the presence of MSI.
12. Is MMR gene a targeted therapy?
No, it is not. It is not appropriate to say that “MMR gene can be targeted after measurement”.