生殖细胞变异,癌症基因 z-bo 2020-09-21 361

　　At present, in order to reduce costs and speed up time, most cancer genetic tests only analyze cancer tissues, not germ cell DNA. Doing so may cause misdiagnosis and misjudgment. This article will conduct a series of analysis and discussion on this issue.

　　According to research conducted by the National Human Genome Research Institute (NHGRI) and the National Cancer Institute (NCI), the mutations obtained by analyzing cancer tissues alone may contain germ cell mutations, which may affect cancer treatment. It is recommended The laboratory is ready for this.

　　The Consortium for Clinical Sequencing Research (CSER) Oncology Working Group was funded by NHGRI and NCI. Its researchers are mainly from the University of Michigan, Harvard University, Ohio State University, University of Pennsylvania, Texas Children’s Cancer Center and Baylor College of Medicine. Developed a series of guidelines for cancer sequencing testing in laboratories, and published some recommendations in the Journal of the National Cancer Institute.

　　According to the CSER working group, if germ cell mutations are not specifically searched during the experiment, once these mutations are identified, they will have an impact on the management of patients and their families. Therefore, laboratories should pay attention to such mutations.

　　Earlier this month, researchers at the Memorial Sloan Kettering Cancer Center reported that an analysis of tumor DNA using a panel containing 341 genes found that 16% of patients had pathogenic germ cell mutations. In addition, many of the mutations detected in patients with cancer risk are actually germ cell mutations. These germ cell variants also affect the treatment of patients and the prediction of cancer risk for their families.

　　In April, researchers at Johns Hopkins University reported that the tumor variants identified in 3% of patients were actually germ cell variants when they were not compared with normal samples for analysis.

　　How to solve the problem?

　　In an article by the CSER working group, the researchers stated: “It is very important that this can be achieved by identifying and inferring germ cell mutations from cancer tissue sequencing results without directly analyzing germ cell DNA.” They Provides such examples and corresponding issues that the laboratory should consider.

　　First of all, cancer panels usually include some recognized genetic cancer mutation genes, such as BRCA1, BRCA2 and Lynch syndrome mutation genes.

　　Secondly, some mutation patterns also suggest potential germ cell mutations. For example, mutations in DNA mismatch repair genes in hypermutant tumors usually indicate germ cell mutations, and large chromosomal rearrangements in pediatric medulloblastoma also imply germ cell TP53 gene mutations.

　　"In addition, many gene mutations can be observed in germ cells and somatic cells. Such genes are usually cancer susceptibility genes, including MSH2, ALK, RB1, TP53 and VHL.

　　Germ cell mutation, clinical attention should be paid

　　Researchers introduced, “In view of the necessity of combining variation analysis and clinical interpretation, we believe that doctors and laboratories should work together to solve the problem of germ cell variation.”

　　The

　　working group also recommended that laboratories that perform cancer panel, exome, or whole-genome sequencing analysis for cancer patients should build a bioinformatics platform to identify germ cell mutations. In addition, laboratories should also develop appropriate strategies to confirm potential germ cell mutations. When formulating this strategy, one should consider: how to obtain germ cell samples from patients; whether the laboratory conducts the test itself or cooperates with a diagnostic agency. In short, the laboratory should develop a standardized method for identifying germ cell variants.

　　In addition, doctors are also responsible for telling patients that this genetic test may find genetic mutations, which will affect their treatment and the assessment of cancer risk for their families. Doctors also need to develop a plan on how to tell patients the results of germ cell mutations.

　　In short, since genetic testing may be affected by germ cell mutations, doctors and laboratories should find effective solutions to reduce misdiagnosis of patients.