Two PMS2 mutations in a Turcot syndrome family with small bowel cancers

Marco Agostini, Maria Grazia Tibiletti, Emanuela Lucci-Cordisco, Annamaria Chiaravalli, Hans Morreau, Daniela Furlan, Luigi Boccuto, Salvatore Pucciarelli, Carlo Capella, Mauro Boiocchi, Alessandra Viel

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Abstract

We report the clinicopathological, genetic, and immunohistochemical characterization of an atypical Turcot syndrome (TS) family with small bowel cancer. The tumor family history of a patient with cafè-au-lait spots (CALS) and early onset adenomas, duodenal cancer, and glioblastoma was positive for colonic adenoma (mother), jejunal (maternal grandfather), lung (father), and colorectal (paternal uncle) cancers. PMS2 genetic testing identified the nonsense 1951C>T (Q643X) and the missense 161C>T (S46I) mutations. PMS2 expression was absent in the proband's duodenal cancer with high microsatellite instability. The normal cells also displayed no PMS2 expression and some degree of instability. Our findings point out the association between PMS2 and TS, and support the hypothesis that patients with a few polyps, small bowel tumors with a very early onset, glioblastoma, and CALS should be considered as a variant of hereditary nonpolyposis colorectal cancer. A recessive model of inheritance caused by compound heterozygous mutations was consistent with the observed severe clinical phenotype and has important implications for predicting cancer risk in both the proband and his relatives.

Original languageEnglish
Pages (from-to)1886-1891
Number of pages6
JournalAmerican Journal of Gastroenterology
Volume100
Issue number8
DOIs
Publication statusPublished - Aug 2005

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Intestinal Neoplasms
Duodenal Neoplasms
Mutation
Glioblastoma
Adenoma
Neoplasms
Mothers
Hereditary Nonpolyposis Colorectal Neoplasms
Microsatellite Instability
Genetic Testing
Polyps
Fathers
Phenotype
Lung
Turcot syndrome

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Agostini, M., Tibiletti, M. G., Lucci-Cordisco, E., Chiaravalli, A., Morreau, H., Furlan, D., ... Viel, A. (2005). Two PMS2 mutations in a Turcot syndrome family with small bowel cancers. American Journal of Gastroenterology, 100(8), 1886-1891. https://doi.org/10.1111/j.1572-0241.2005.50441.x

Two PMS2 mutations in a Turcot syndrome family with small bowel cancers. / Agostini, Marco; Tibiletti, Maria Grazia; Lucci-Cordisco, Emanuela; Chiaravalli, Annamaria; Morreau, Hans; Furlan, Daniela; Boccuto, Luigi; Pucciarelli, Salvatore; Capella, Carlo; Boiocchi, Mauro; Viel, Alessandra.

In: American Journal of Gastroenterology, Vol. 100, No. 8, 08.2005, p. 1886-1891.

Research output: Contribution to journalArticle

Agostini, M, Tibiletti, MG, Lucci-Cordisco, E, Chiaravalli, A, Morreau, H, Furlan, D, Boccuto, L, Pucciarelli, S, Capella, C, Boiocchi, M & Viel, A 2005, 'Two PMS2 mutations in a Turcot syndrome family with small bowel cancers', American Journal of Gastroenterology, vol. 100, no. 8, pp. 1886-1891. https://doi.org/10.1111/j.1572-0241.2005.50441.x
Agostini M, Tibiletti MG, Lucci-Cordisco E, Chiaravalli A, Morreau H, Furlan D et al. Two PMS2 mutations in a Turcot syndrome family with small bowel cancers. American Journal of Gastroenterology. 2005 Aug;100(8):1886-1891. https://doi.org/10.1111/j.1572-0241.2005.50441.x
Agostini, Marco ; Tibiletti, Maria Grazia ; Lucci-Cordisco, Emanuela ; Chiaravalli, Annamaria ; Morreau, Hans ; Furlan, Daniela ; Boccuto, Luigi ; Pucciarelli, Salvatore ; Capella, Carlo ; Boiocchi, Mauro ; Viel, Alessandra. / Two PMS2 mutations in a Turcot syndrome family with small bowel cancers. In: American Journal of Gastroenterology. 2005 ; Vol. 100, No. 8. pp. 1886-1891.
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