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

Ie Ming Shih, Hui Yan, David Speyrer, Barry M. Shmookler, Paul H. Sugarbaker, Brigitte Maria Ronnett

Research output: Contribution to journalArticle

Abstract

Pseudomyxoma peritonei (PMP) is a clinical syndrome characterized by mucinous 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 evidence that the peritoneal lesions in PMP are clonally derived from the associated appendiceal adenoma. Little is known about the molecular genetic alterations or hereditary factors involved in the development of appendiceal mucinous tumors and PMP. We report the only known example of appendiceal mucinous adenomas in identical twin brothers, one of whom developed PMP. We analyzed the status of the K-RAS and APC genes in these tumors using digital polymerase chain reaction and digital single nucleotide polymorphism (SNP) assay. Identical K-RAS mutations were detected in the appendiceal adenoma and peritoneal tumor from the twin with PMP, whereas the adenoma from the other twin harbored a different mutation. Digital SNP analysis demonstrated loss of heterozygosity of APC only in the adenoma from the twin without PMP but not from the appendiceal or peritoneal tumors of the twin with PMP. The adjacent normal tissue in each case retained both APC alleles. The K-RAS mutational analysis supports the view that PMP is clonally derived from the associated appendiceal mucinous adenoma. The lack of loss of heterozygosity of APC in the adenoma and peritoneal tumor from the twin with PMP suggests that loss of heterozygosity of APC is not necessarily involved in the development 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 from both twins suggest that mutation in K-RAS and loss of heterozygosity of APC occurs somatically in adenomas and is independent of the identical genetic background of the twins.

Original languageEnglish (US)
Pages (from-to)1095-1099
Number of pages5
JournalAmerican Journal of Surgical Pathology
Volume25
Issue number8
DOIs
StatePublished - 2001

Fingerprint

Pseudomyxoma Peritonei
Monozygotic Twins
Adenoma
Molecular Biology
Loss of Heterozygosity
Neoplasms
Mutation
Single Nucleotide Polymorphism
APC Genes
Mucins
Ascites
Siblings
Epithelium
Alleles

Keywords

  • Appendix
  • Molecular genetic analysis
  • Mucinous adenoma
  • Pseudomyxoma peritonei

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine

Cite this

Molecular genetic analysis of appendiceal mucinous adenomas in identical twins, including one with pseudomyxoma peritonei. / Shih, Ie Ming; Yan, Hui; Speyrer, David; Shmookler, Barry M.; Sugarbaker, Paul H.; Ronnett, Brigitte Maria.

In: American Journal of Surgical Pathology, Vol. 25, No. 8, 2001, p. 1095-1099.

Research output: Contribution to journalArticle

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abstract = "Pseudomyxoma peritonei (PMP) is a clinical syndrome characterized by mucinous 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 evidence that the peritoneal lesions in PMP are clonally derived from the associated appendiceal adenoma. Little is known about the molecular genetic alterations or hereditary factors involved in the development of appendiceal mucinous tumors and PMP. We report the only known example of appendiceal mucinous adenomas in identical twin brothers, one of whom developed PMP. We analyzed the status of the K-RAS and APC genes in these tumors using digital polymerase chain reaction and digital single nucleotide polymorphism (SNP) assay. Identical K-RAS mutations were detected in the appendiceal adenoma and peritoneal tumor from the twin with PMP, whereas the adenoma from the other twin harbored a different mutation. Digital SNP analysis demonstrated loss of heterozygosity of APC only in the adenoma from the twin without PMP but not from the appendiceal or peritoneal tumors of the twin with PMP. The adjacent normal tissue in each case retained both APC alleles. The K-RAS mutational analysis supports the view that PMP is clonally derived from the associated appendiceal mucinous adenoma. The lack of loss of heterozygosity of APC in the adenoma and peritoneal tumor from the twin with PMP suggests that loss of heterozygosity of APC is not necessarily involved in the development 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 from both twins suggest that mutation in K-RAS and loss of heterozygosity of APC occurs somatically in adenomas and is independent of the identical genetic background of the twins.",
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