PAX8

Overview

PAX8 (Paired Box 8) encodes a transcription factor critical for renal and thyroid lineage specification. In ccRCC biology, PAX8 drives renal proximal tubule identity and cooperates with HIF2A (EPAS1) to regulate cyclin D1 (CCND1) expression. It is used as a lineage marker in mouse models of VHL-associated oncogenesis.

Alterations observed in the corpus

  • PAX8 used as the lineage-restricted Cre driver (Pax8-CreERT2) to achieve proximal tubule-specific conditional Vhl inactivation in a mouse ccRCC model; 95.7% of recombined (tdTomato+) cells were PT S1/S2/S3. Prior work cited in this study (Patel 2022) showed HIF2A cooperates with PAX8 to upregulate CCND1 in ccRCC PMID:23797736
  • PAX8/PPARG fusion detected in 4/484 (0.8%) papillary thyroid carcinomas (PTCs); PAX8 is the 5’ fusion partner; these tumors exhibit a RAS-like (RL) expression phenotype and are mutually exclusive with BRAF/RAS/EIF1AX mutations. PI3K/PPARγ pathway alterations (PTEN, AKT1/2, PAX8/PPARG) found in 4.5% (18/402) of PTCs. PMID:25417114
  • PAX8 found fused to PPARG in 3 PDTCs in a targeted-sequencing study of poorly differentiated and anaplastic thyroid cancers (PDTC/ATC); fusion recapitulates the PAX8-PPARG rearrangement previously described in follicular thyroid carcinoma. PMID:26878173

Cancer types (linked)

  • Clear cell renal cell carcinoma (ccRCC): PAX8 is a renal lineage TF and HIF2A cooperating factor in this tumor context PMID:23797736

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • No direct therapeutic nominations for PAX8 in the corpus; HIF2A antagonism (belzutifan) is nominated as a strategy in VHL disease, in a setting where PAX8-expressing proximal tubule cells are the cancer cells-of-origin PMID:23797736

Open questions

  • The precise PAX8 target gene repertoire cooperating with HIF2A in early VHL-null PT cell proliferation/dedifferentiation remains to be mapped.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:25417114

This page was processed by crosslinker on 2026-05-14. - PMID:26878173

This page was processed by wiki-cli on 2026-05-14.