Sixteen significantly mutated genes were discerned in this molecular subgroup (Table 1): 9 genes previously implicated in endometrial cancer (PTEN, PIK3CA, CTNNB1, ARID1A, PIK3R1, KRAS, FGFR2, CHD4, SPOP) by us and others [(17, 18); reviewed in (24)], and 7 genes (BCOR, CSMD3, CTCF, MECOM, METTL14, SGK1, SOX17) not previously recognized to have a role in endometrial tumorigenesis.
That is not to say that chromatin-remodeling genes and genes of the ubiquitin ligase complex are not also perturbed in the endometrioid subtype; indeed, a number of chromatin-remodeling genes, such as ARID1A, ARID5B, CTCF, and CHD4, are also causal or candidate driver genes in molecular subgroups dominated by endometrioid endometrial tumors (Table 1).
The researchers speculated that ARID1A functions as a tumor suppressor gene and, when mutated, is "likely to directly lead to epigenetic changes in cancer cells.
The four genes with the most prevalent mutations were PIK3CA and KRAS, which had been previously linked to ovarian clear cell carcinoma, and ARID1A and PPP2R1A, which had not.
With more than 100,000 new cases worldwide of stomach cancer each year likely to be caused by mutations in FAT4 or ARID1A
, drugs against these targets may someday lead to more effective treatment of stomach tumours and other cancers.
Loss of ARID1A staining was seen in 12 of 120 EACs (10%), with complete loss of staining in the entire tumor in 10 of 12 cases (83%) and in a discrete, confluent focus in 2 of 12 (17%) cases.
Loss of MLH1 expression was present in 2 of 12 cases (17%) with ARID1A loss but in none of the ARID1A-intact tumors.
Several important genes in gynecologic cancers--for example, PTEN, ARID1A
, and HER2/neu--may exhibit somatic mutations in numerous regions of the gene, making a sequencing-based approach more attractive than hotspot testing or single-nucleotide genotyping.
p53, p16, PTEN, ARID1A (BAF250), and DNA MMR (PMS2, MSH6).
A useful diagnostic panel includes p53, PTEN, ARID1A, and DNA MMR.
Recently, loss of BAF250a has been found in a subset of pure clear cell endometrial carcinoma, suggesting the role of ARID1A gene in its pathogenesis.
Does the loss of ARID1A (BAF-250a) expression in endometrial clear cell carcinomas have any clinicopathologic significance?