Post written by Darina Kohoutova from the 2nd Department of Internal Medicine – Gastroenterology, Charles University in Praha, Faculty of Medicine at Hradec Kralove, University Teaching Hospital, Hradec Kralove, Czech Republic

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) has to date been recognized in only 8 families worldwide. Recently, different point mutations within the Ying Yang 1 (YY1) binding motif in promoter 1B of the APC gene were assigned as causal in 6 families with GAPPS.

We diagnosed GAPPS across 3 generations of a Czech Caucasian family. Three members of this family died of gastric adenocarcinoma. The youngest female family member died at the age of 26.

All 5 members of 3 generations had polyposis involving exclusively the gastric fundus and body, with relative sparing of the lesser curve (Figure 1). Four of 5 members (members of the second and the third generation) were surveilled endoscopically. Still, 2 of them died of gastric adenocarcinoma. Two members of the third generation were saved having undergone total gastrectomy. Histology of surgical specimens showed gastric adenocarcinoma stage IA (pT1a, N0, M0) in both cases. As the original GAPPS criteria need to be met,¹ we ruled out all other types of gastric polyposes and other hereditary gastrointestinal syndromes (endoscopically and by genetic testing). Having followed a recent article written by Li et al,² the promoter 1B was scrutinized by Sanger sequencing of a PCR product covering the YY1 motif. A point mutation (c.-191 T>C) was detected in all 3 tested samples.

Figure 1: Polyposis involving exclusively the gastric fundus and body, with relative sparing of the lesser curve.

Atypical endoscopic progression of the fundic gland polyposis, with the presence of dysplasia on polypectomy specimens and genetic testing with recently discovered mutations in promoter 1B of APC gene might help clinicians determine whether prophylactic gastrectomy should be performed.

1. Worthley DL, Phillips KD, Wayte N, et al. Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome. Gut 2012;61:774-9.
2. Li J, Woods SL, Healey S, et al. Point mutations in exon 1B of APC reveal gastric adenocarcinoma and proximal polyposis of the stomach as a familial adenomatous polyposis variant. Am J Hum Genet 2016;98(5):830-42.

Find the article abstract here.

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