The Cancer Genome Atlas proposes classification based on the genomic profile which relates to patient outcome, except which one?

• A. p63
• B. MMR
• C. POLE
• D. PTEN

Answer: (A)

This question centers on how The Cancer Genome Atlas (TCGA) defines cancer subtypes by genomic alterations that relate to prognosis. In the framework most often discussed for endometrial and related cancers, TCGA classifies tumors into four molecular groups: tumors with POLE ultramutations (excellent prognosis), tumors with mismatch repair deficiency leading to microsatellite instability (MSI-H), tumors with low copy-number alterations (often with PTEN pathway alterations), and tumors with high copy-number changes resembling serous cancers (TP53-mutant, poorer outcome). A marker like p63, a transcription factor used to identify squamous differentiation, is not part of this genomic-based stratification and does not define a TCGA prognostic subgroup. Therefore, p63 is the correct exception. MMR status and POLE mutations are direct classifier features, and PTEN-related alterations commonly appear within the copy-number low group, reflecting the broader profile rather than forming a separate category.