Immunotherapy by Unknown

Immunotherapy by Unknown

Author:Unknown
Language: eng
Format: epub
ISBN: 9783030410087
Publisher: Springer International Publishing


Endometrial Cancer

Following the published results by the Cancer Genome Atlas Research Network, contemporary classification of endometrial cancer has shifted away from the traditional two histologic types (endometrioid vs. non-endometrioid; sometimes referred to as type I and type II cancers) and towards four types based on genomic sequencing: DNA polymerase epsilon (POLE) ultramutated, microsatellite instability hypermutated (MSI-H), copy-number low, and copy-number high [18]. Microsatellites are repeated sequences of DNA that become sites of DNA replication errors with “microsatellite instability” occurring in the setting of defects in the DNA mismatch repair (MMR) pathway. Defects of MMR function result in MSI in approximately 20–30% of endometrial tumors [18, 19]. Loss of MMR function is typically due to sporadic hypermethylation of the MLH1 promotor and less frequently due to germline mutations (i.e., hereditary nonpolyposis colon cancer (HNPCC) syndrome, also known as Lynch syndrome) [18, 20]. MMR-deficient and POLE-mutant endometrial tumors display a high number of tumor-infiltrating lymphocytes as well as a high neoantigen load (due to high somatic tumor DNA mutational burden) giving the potential to elicit a strong antitumor immune response [18, 21–23].



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