Adenomatous polyposis coli promoter abnormalities in familial adenomatous polyposis and gastric adenocarcinoma and proximal polyposis of the stomach

Figure 1 Flow diagram summarizing the processes of identification, screening, eligibility, and exclusion of the literature search. APC: Adenomatous polyposis coli.

Figure 2 Schematic representation of the adenomatous polyposis coli promoter 1B-1A region and proposed mechanisms underlying the phenotypic divergence of promoter-associated variants. A: The relative positions of promoter 1B, exon 1B, promoter 1A, and exon 2 are shown with approximate genomic distances. Class I-IV alterations are mapped according to their reported extents. Promoters 1A and 1B give rise to distinct adenomatous polyposis coli (APC) transcripts with alternative non-coding first exons (5′ untranslated regions). The representative RefSeq transcripts are NM_000038.6 (promoter 1A-derived) and NM_001127511.3 (promoter 1B-derived); B: Expanded view of the APC promoter 1B Yin Yang 1 (YY1)-binding region. The closely adjacent variants within this region have been associated with distinct clinical phenotypes, including phenotypes that are predominantly gastric (gastric adenocarcinoma and proximal polyposis of the stomach), predominantly colorectal (familial adenomatous polyposis), and mixed. The YY1-binding site is indicated within the promoter 1B region. The schematic illustrates the potential mechanisms linking these variants to phenotypic diversity, including an altered YY1-dependent transcription, tissue-specific regulation (e.g., promoter 1A methylation), and residual APC activity differences. These mechanisms are presented as a conceptual model, as the precise molecular basis of phenotypic divergence remains unclear. APC: Adenomatous polyposis coli; YY1: Yin Yang 1; GAPPS: Gastric adenocarcinoma and proximal polyposis of the stomach; FAP: Familial adenomatous polyposis.