Fig. 4.

Types of ARID1A mutations and correlation of mutation and protein expression. A. Analysis of reported ARID1A mutations demonstrates that most of the mutation types belong to frameshift, nonsense, and in-frame mutations that are associated with loss of the tumor suppressor functions of ARID1A. B. ARID1A mutational status in 27 uterine endometrioid carcinomas. All the tumors with ARID1A mutation (in one or both alleles) have lost ARID1A immunoreactivity, and interestingly, two of 15 ARID1A wildtype cases also lost ARID1A staining probably due to epigenetic inactivation. Occasionally, clonal loss of ARID1A expression, as defined by undetectable ARID1A immunoreactivity contiguous to ARID1A positive tumor areas, is found in tumors harboring ARID1A mutations, probably as a result of intra-tumoral heterogeneity. Red boxes denote ARID1A mutation in both alleles (allele 1 and allele 2). Red boxes in the column of ARID1A staining indicate a complete loss (dark red) or clonal loss (light red) of ARID1A expression. Examples of ARID1A staining from two tumors are shown. Asterisk: the tumor area showing clonal loss of ARID1A staining.