Alleles of the APC gene: An attenuated form of familial polyposis

Spirio, Lisa; Olschwang, Sylviane; Groden, Joanna; Robertson, Margaret; Samowitz, Wade S.; Joslyn, Geoff; Gelbert, Lawrence M.; Thliveris, Andrew; Carlson, Margaret; Otterud, Brith; Lynch, Henry T.; Watson, Patrice; Lynch, Patrick M.; Laurent‐Puig, Pierre; Burt, Randall W.; Hughes, Jaime; Thomas, Gilles; Leppert, M.; White, Ray

doi:10.1016/0092-8674(93)90538-2

Cited by 552 publications

(247 citation statements)

References 27 publications

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“…Germline mutations between codons 168 and 1680 (Sieber et al, 2000) and whole APC deletions (De Rosa et al, 1999;Sieber et al, 2002) are associated with classical FAP. Attenuated phenotypes, characterized by a few polyps (about 10-100), are associated with mutations at the extreme 5' or 3'ends of the APC gene or in alternatively spliced exon 9 (Nagase et al, 1992;van der Luijt et al, 1996;Spirio et al, 1993;Soravia et al, 1998). FAP patients may also develop extracolonic manifestations.…”

Section: Introductionmentioning

confidence: 99%

First genotype characterization of Argentinean FAP patients: Identification of 14 novelAPCmutations

Rosa¹,

Dourisboure

Morelli³

et al. 2004

Hum. Mutat.

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We examined the adenomatous polyposis coli (APC) gene for disease-causing mutations in 51 unrelated Argentinean probands affected by familial adenomatous polyposis (FAP).Using a combination of the protein truncation test, the single strand conformation polymorphism technique, DNA sequencing and quantitative PCR analysis, we identified the specific mutation in 39 (average age: 28.4 years) of the 51 probands (detection rate: 76.47%); 13 are novel germline mutations and one is a novel sequence variant. There were 27 small deletions, four small duplications, five nonsense mutations in exon 15, three nonsense mutations in exons 6, 11, and 12, and one sequence variant in exon 3 identified in a patient bearing a truncating mutation in exon 15. The most common mutation (found in 10 cases) was at codon 1309. All patients negative for APC mutations were also negative for the MutY homolog (MYH) gene mutation, as expected because of fully penetrant FAP cases. This study enlarges the spectrum of APC gene mutations, and reinforces the concept of mutation heterogeneity. It also sheds light on correlations between the site of APC germline mutations and the clinical manifestations of FAP. Our data indicate that the genotype/phenotype correlations in Argentinean patients are similar to those observed in other populations.

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Section: Introductionmentioning

confidence: 99%

First genotype characterization of Argentinean FAP patients: Identification of 14 novelAPCmutations

Rosa¹,

Dourisboure

Morelli³

et al. 2004

Hum. Mutat.

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“…In desmoids and uppergastrointestinal tumours, LOH is associated with germline APC mutations between the second and third 20AARs, and the optimum mutant proteins appear to encode a total of three or four 20AARs. Another manifestation of the requirement for optimal Wnt signalling in colorectal tumorigenesis is the existence of attenuated disease (AFAP) (Spirio et al, 1993). Although the division between classical FAP and AFAP is indistinct (Knudsen et al, 2003), in the latter, patients typically have fewer than 100 colorectal adenomas at presentation.…”

Section: Selective Constraints On Apc Mutations In Inherited and Spormentioning

confidence: 99%

Colorectal cancer and genetic alterations in the Wnt pathway

2006

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“…FAP families are defined as attenuated (AAPC) when the number of polyps is less than 100 in some of the patients (belonging to the same family) and the mean age at diagnosis is older as compared to that recorded in the classical FAP patients. 1 The gene responsible for the vast majority of FAP cases, the APC gene, was cloned in 1991. 2 Since then, over 826 germline mutations have been found in families with FAP.…”

mentioning

confidence: 99%

Prevalence of the Y165C, G382D and 1395delGGA germline mutations of the MYH gene in Italian patients with adenomatous polyposis coli and colorectal adenomas

Gismondi

Meta²,

Bonelli³

et al. 2004

Intl Journal of Cancer

156

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Biallelic germline mutations in the base excision repair gene MYH have been reported in patients with multiple colorectal adenomas and cancer and in sporadic FAP patients not showing a detectable APC germline mutation. In this study, the prevalence of the common Y165C and G382D germline variants of the MYH gene was examined in 70 FAP/AAPC patients with no detectable APC mutation and a family history compatible with recessive inheritance. In addition, 141 normal-population adenoma patients (mean number of adenomas, 2.8; range, 1-9) and 52 clean colon controls were studied. The entire coding region of the MYH gene was analyzed in Y165C or G382D heterozygous patients. Since the same second mutational event (a 3 bp deletion in exon 14, 1395delGGA) was detected in 3 patients, the prevalence of this variant was also examined in all groups. In all, 14 of 70 patients in the FAP/AAPC group (20%; 95% CI ‫؍‬ 11.7-31.6%) had biallelic germline MYH variants and 3 were heterozygotes (4.3%). None of the 141 normal-population adenoma patients carried biallelic germline MYH variants (95% CI ‫؍‬ 0.06 -4.1%) and 3 were heterozygotes (2.1%). In the control group, no MYH variants were detected. These results indicated that MYH-associated polyposis (MAP) is present in about 20% of Italian FAP/AAPC patients, in whom no germline APC mutation is detectable and showing a family history compatible with recessive inheritance, and in a small fraction of patients with colorectal adenomas in the general population. In addition, our data suggest that mutation 1395delGGA is a subpolymorphic MYH mutational event in some Caucasian populations.

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Alleles of the APC gene: An attenuated form of familial polyposis

Cited by 552 publications

References 27 publications

First genotype characterization of Argentinean FAP patients: Identification of 14 novelAPCmutations

First genotype characterization of Argentinean FAP patients: Identification of 14 novelAPCmutations

Colorectal cancer and genetic alterations in the Wnt pathway

Prevalence of the Y165C, G382D and 1395delGGA germline mutations of the MYH gene in Italian patients with adenomatous polyposis coli and colorectal adenomas

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