Molecular genetic analysis of appendiceal mucinous adenomas in identical twins, including one with pseudomyxoma peritonei

Pseudomyxoma peritonei (PMP) is a clinical syndrome characterized by mucino us. ascites and peritoneal lesions composed of histologically bland to low- grade adenomatous mucinous epithelium within pools of extracellular mucin, often with an associated mucinous. adenoma of the appendix. There is eviden ce that the peritoneal lesions in PMP are clonally derived from the associa ted appendiceal adenoma. Little is known about the molecular genetic altera tions or hereditary factors involved in the development of appendiceal muci nous tumors and PMP. We report the only known example of appendiceal mucino us. adenomas in identical twin brothers, one of whom developed PMP. We anal yzed the status of the K-RAS and APC genes in these tumors using digital po lymerase chain reaction and digital single nucleotide polymorphism (SNP) as say. Identical K-RAS mutations were detected in the appendiceal adenoma and peritoneal tumor from the twin with PMP, whereas the adenoma from the othe r twin harbored a different mutation. Digital SNP analysis demonstrated los s of heterozygosity of APC only in the adenoma from the twin without PMP bu t not from the appendiceal or peritoneal tumors of the twin with PMP. The a djacent normal tissue in each case retained both APC alleles. The K-RAS mut ational analysis supports the view that PMP is clonally derived from the as sociated appendiceal mucinous adenoma. The lack of loss of heterozygosity o f APC in the adenoma and peritoneal tumor from the twin with PMP suggests t hat loss of heterozygosity of APC is not necessarily involved in the develo pment of all appendiceal adenomas or PMP. The different types of mutations in K-RAS and the different allelic status of the APC locus in the tumors fr om both twins suggest that mutation in K-RAS and loss of heterozygosity of APC occurs somatically in adenomas and is independent of the identical gene tic background of the twins.