Rare mutations predisposing to familial adenomatous polyposis in Greek FAP patients

Mihalatos, Markos; Apessos, Angela; Dauwerse, Hans G.; Velissariou, Voula; Psychias, Aristidis; Koliopanos, Alexander; Πετρόπουλος, Κωνσταντίνος; Triantafillidis, John K.; Danielidis, I; Fountzilas, George; Agnantis, Niki J.; Nasioulas, Georgios

doi:10.1186/1471-2407-5-40

Cited by 14 publications

(10 citation statements)

References 34 publications

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“…The large APC gene rearrangements were identified in 26 patients, and 12 of them were deletions of the whole APC gene (Aretz et al 2005). In Greek patients, only one large rearrangement in 25 studied families was detected (Mihalatos et al 2005), while in another study in Belgium, 4 large rearrangements were revealed in 27 examined FAP families, and 3 of them were deletions of the whole APC gene (Michils et al 2005). In the German and Belgian groups, the percentage of large rearrangements was almost equal (15%), but in the Greek group it was 4%.…”

Section: Discussionmentioning

confidence: 99%

APC gene mutations causing familial adenomatous polyposis in Polish patients

Pławski

Słomski

2008

J Appl Genet

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Familial adenomatous polyposis (FAP) is a well-known hereditary condition characterised by alimentary system tumours. Tens to thousands of polyps occur in the colon and rectum of the patients. There is a high heterogeneity with regard to the number and time of the occurrence of polyps. The occurrence of FAP is associated with mutations in the APC tumour suppressor gene, which was described in 1991. Since then, many studies have been done to analyse the distribution of mutations in individual populations and to determine the function of the gene and a diagnostic approach to FAP. Here the APC gene was studied with respect to the occurrence of small mutations and large rearrangements in 300 unrelated Polish FAP families. Ninety-seven mutations were identified in 164 families. Out of these mutations, 80 were small mutations, including 58 small mutations that were first identified in the Polish population (42 novel and 16 described previously). An increased frequency of mutation c.3927_3931delAAAGA was observed in 10% of the Polish group. Seventeen large rearrangements were found in 29 families. Out of those rearrangements, 8 repeat rearrangements occurred in 20 families. A problem in fast molecular diagnostics of FAP is a high heterogeneity of mutations in the APC gene. It seems that a multiplex ligation-dependent probe amplification test and searching for small mutations by the use of screening methods at the 5' end of exon 15 and exons 14, 9, 11, 13, 5, and 3, help to improve the molecular diagnostics of FAP in Polish patients.

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Section: Discussionmentioning

confidence: 99%

APC gene mutations causing familial adenomatous polyposis in Polish patients

Pławski

Słomski

2008

J Appl Genet

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“…The three nonsense mutations, one missense (p.Ile1307Lys) mutation and the other polymorphism (p.Thr1493Thr) were published before. Two of them (p.Ser1315Stop, p.Ile1307Lys) are characteristic of the Ashkenazi population [28][29][30][31][32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

Somatic APC Inactivation Mechanisms in Sporadic Colorectal Cancer Cases in Hungary

Kámory

Olasz

Csuka

2008

Pathol. Oncol. Res.

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The role of germline inactivation of the adenomatosis polyposis coli (APC) gene in hereditary colorectal cancer is well known, being the most important cause of familial adenomatosus polyposis (FAP) syndrome. Hereditary cases with germline mutations, however, account only for 5-10% of colorectal cancers. The somatic inactivation of this gene has also been observed in sporadic cases. In order to examine the inactivation mechanisms of the APC gene we screened 70 sporadic colorectal cancer cases (27 rectal, 43 intestinal) of different stages for promoter hypermethylation, allelic imbalance (AI) and somatic mutations. The presence of promoter hypermethylation was observed in 21 cases (30%). Fifteen of the examined tumors (21%) showed AI, and also 15 tumors (21%) carried at least one somatic mutation. Thirteen of the detected alterations were novel variations: seven frameshifts, four missense mutations and two polymorphisms. Biallelic inactivation was found in 15 patients (21%). These results suggest that the inactivation of the APC gene is very common in sporadic colorectal cancer, and the main inactivation mechanism of the APC gene is promoter hypermethylation. Allelic imbalance has the same frequency as mutations, and mutations in the APC gene are more common in the early stages and in tumors located in the rectum.

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“…Linkage analysis to markers on chromosome 5q, protein tr uncation testing, direct sequencing, conformation-sensitive gel electrophoresis, and single-strand, conformation-sensitive gel electrophoresis all have accuracies 70%-90% [30] . Splice site defects or gross genomic alterations may have been underestimated by the older testing methods and require cDNA screening and gene rearrangement testing [31] . Genetic risk assessment should precede the initiation of regular endoscopic screening [32] .…”

Section: Discussionmentioning

confidence: 99%

Gardner's syndrome: Genetic testing and colonoscopy are indicated in adolescents and young adults with cranial osteomas: A case report

Smuđ

Augustin²,

Kekez³

et al. 2007

WJG

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We present a case of a 25-year-old female with diagnosed familial adenomatous polyposis and elevated carcinoembryonic antigen with negative family history. The suspicion of Gardner's syndrome was raised because extirpation of an osteoma of the left temporo-occipital region was made 10 years ago. Restorative proctocolectomy and ileal pouch anal anastomosis was made but histology delineated adenocarcinoma of the rectum (Dukes C stage). We conclude that cranial osteomas often precede gastrointestinal manifestations of familial adenomatous polyposis or Gardner's syndrome and such patients should be evaluated with genetic testing followed by colonoscopy if results are positive to prevent the development of colorectal carcinoma. If the diagnosis is positive all family members should be evaluated for familial adenomatous polyposis.

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Rare mutations predisposing to familial adenomatous polyposis in Greek FAP patients

Cited by 14 publications

References 34 publications

APC gene mutations causing familial adenomatous polyposis in Polish patients

APC gene mutations causing familial adenomatous polyposis in Polish patients

Somatic APC Inactivation Mechanisms in Sporadic Colorectal Cancer Cases in Hungary

Gardner's syndrome: Genetic testing and colonoscopy are indicated in adolescents and young adults with cranial osteomas: A case report

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