title: Disruption of the APC gene by t(5;7) translocation in a Turcot family.
abstract: Turcot syndrome (TS) refers to the combination of colorectal polyps and primary tumours of the central nervous system. TS is a heterogeneous genetic condition due to APC and/or mismatch repair germline mutations. When APC is involved the vast majority of mutations are truncating, but in approximately 20%-30% of patients with familial polyposis no germline mutation can be found. A 30-year-old Caucasian woman with a positive pedigree for TS was referred to our Genetic Counselling Service. She was negative for APC and MUTYH but showed a reciprocal balanced translocation t(5;7)(q22;p15) at chromosome analysis. FISH analysis using specific BAC probes demonstrated that 5q22 breakpoint disrupted the APC gene. Transcript analysis by MLPA and digital PCR revealed that the cytogenetic rearrangement involving the 3' end of the APC gene caused a defective expression of a truncated transcript. This result allowed cytogenetic analysis to be offered to all the other family members and segregation analysis clearly demonstrated that all the carriers were affected, whereas non-carriers did not have the polyposis. A cytogenetic approach permitted the identification of the mutation-causing disease in this family, and the segregation analysis together with the transcript study supported the pathogenetic role of this mutation. Karyotype analysis was used as a predictive test in all members of this family. This family suggests that clinically positive TS and FAP cases, which test negative with standard molecular analysis, could be easily and cost-effectively resolved by a classical and molecular cytogenetic approach.
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, via O. Rossi 9, IT-21100 Varese, Italy. Electronic address: n.sahnane@gmail.com.
authors.forename: Nora
authors.initials: N
authors.lastname: Sahnane
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, via O. Rossi 9, IT-21100 Varese, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bernasconi
authors.affiliation: Ospedale di Circolo di Varese, Unit of Pathology, via O. Rossi 9, IT-21100 Varese, Italy.
authors.forename: Ileana
authors.initials: I
authors.lastname: Carnevali
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, via O. Rossi 9, IT-21100 Varese, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Furlan
authors.affiliation: CRO Aviano National Cancer Institute, Unit of Experimental Oncology 1, via F. Gallini 2, IT-33081 Aviano, PN, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Viel
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, via O. Rossi 9, IT-21100 Varese, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Sessa
authors.affiliation: Ospedale di Circolo di Varese, Unit of Pathology, via O. Rossi 9, IT-21100 Varese, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Tibiletti
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5; D002897:Chromosomes, Human, Pair 7; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D017491:Genes, APC; D006801:Humans; D007621:Karyotyping; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D014178:Translocation, Genetic
keywords: APC; FISH; MLPA; Turcot syndrome; conventional karyotype; digital PCR