Genotype and phenotype factors as determinants of desmoid tumors in patients with familial adenomatous polyposis

Bertario, Lucio; Russo, Antonio; Sala, Paola; Eboli, M.; Giarola, Monica; D’Amico, F.; Gismondi, Viviana; Varesco, Liliana; Pierotti, Marco A.; Radice, Paolo

doi:10.1002/1097-0215(20010320)95:2<102::aid-ijc1018>3.0.co;2-8

Cited by 206 publications

(187 citation statements)

References 45 publications

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“…To date, several factors have been suggested as risks for desmoid tumors in FAP patients. Surgical trauma has been shown to be the most important desmoid-inducing factor (Friedl et al, 2001), followed by APC mutations beyond codon 1444, family history of desmoid tumor, presence of osteoma, female gender and a frameshift mutation in codon 1924 (Bertario L et al, 2001;Eccles DM et al, 1996). However, the mechanisms of desmoid tumor formation are not yet fully understood.…”

Section: Resultsmentioning

confidence: 99%

Mutation spectrum of the APC gene in 83 Korean FAP families

Kim

Kang

et al. 2005

Hum. Mutat.

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Familial adenomatous polyposis (FAP) is a clinically well-defined hereditary disease caused by germline mutations in the adenomatous 1438C>T, c.2232_2233dupCT, c.3426delT, c.3739_3769del31, c.3931_3935delATTGG, c.4332dupA, and c.4722_4725delACTA. Desmoid tumors were identified in 6 of the examined FAP patients, five of whom had APC germline mutations; these mutations involved codons 849, 864, 1309, 1444 and 1464, respectively (c.2547_2548delTA, c.2592_2593insCT, c.3927_3931delAAAGA, c.4332dupA and c.4391-4394delAGAG). Four of the included FAP patients had papillary thyroid cancers; all were female and had germline APC mutations (c.1863_1865delTTAincCT, c.2805C>A, c.3183_3187delACAAA and c.3927_3931delAAAGA).

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Section: Resultsmentioning

confidence: 99%

Mutation spectrum of the APC gene in 83 Korean FAP families

Kim

Kang

et al. 2005

Hum. Mutat.

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“…Although desmoid tumours do not metastasise, they tend to be locally invasive. The aetiology is not exactly known, but the association with familial adenomatous polyposis coli (FAP), as well as with previous trauma, has been extensively described [1,2].…”

Section: Discussionmentioning

confidence: 99%

A 20-year-old male with thoracic pain and a lower thoracic mass

Jong

Graaf²,

Jagt³

et al. 2005

European Respiratory Journal

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A 20-yr-old Caucasian male construction worker had a previous history of a road traffic accident 3 yrs before presentation. A computed tomography (CT) scan of the thoracic spine was carried out to exclude vertebral damage. No evidence of vertebral bone damage or other lesions was seen, and the patient recovered without sequelae.A week before presentation, he noticed a stabbing pain in his right hemithorax, without dyspnoea. The pain persisted, and the patient was referred, by his general practitioner, for a chest radiograph ( fig. 1). Based on these results, the patient was referred to a general hospital for further diagnostic tests. A CT scan of thorax and abdomen (not shown) revealed a large mass, which was interpreted to arise in the right upper abdomen, probably originating from the liver. A malignant tumour, or a metastatic lesion, was suspected and the patient was referred to University Medical Center Groningen (Groningen, The Netherlands).The patient did not suffer from dyspnoea, cough or haemoptysis and there was no history of fever, weight loss, fatigue or excessive sweating. There were no neurological or gastrointestinal complaints. The patient was a nonsmoker, and did not use any medication.On physical examination, a healthy appearing, haemodynamically stable young male, of normal posture was seen. On percussion, a dull sound was found in the right lower zone of the chest. Auscultation revealed normal cardiac sounds without murmurs, and normal breathing sounds on the left side and upper right side of the chest. Abdominal examination revealed no palpable masses or other abnormalities. No palpable lymph nodes were present. Additional physical examination revealed no other abnormalities.Laboratory tests only showed a slightly elevated serum alkaline phosphatase of 174 U?L -1 (normal value: 13-120 U?L -1 ). Serum lactate dehydrogenase, a-fetoprotein and b-human chorionic gonadotropin values were all normal; therefore, an extra-gonadal germ cell tumour was unlikely.On revision of the CT scan, there was doubt regarding the hepatic origin of the mass. Therefore, abdominal ultrasonography was performed. No focal lesions in the liver parenchyma were observed, and the liver blood flow appeared intact. In the right thoracic region, a mass was seen with variable echogenicity and rich vascularisation. Due to the high degree of vascularisation observed on the abdominal ultrasonography, no percutaneous biopsy was performed. A CT angiography was performed: first, to narrow the differential diagnosis, and, secondly, to provide the thoracic surgeon with more detailed information about vascularisation ( fig. 2). At bronchoscopy, no endobronchial abnormalities were seen. Cytological examination of the bronchial lavage showed no signs of malignancy. A bone scan was normal.Exploratory thoracotomy revealed a tumour originating from the right dorsal region, lateral from the vertebral column. A surgeon was able to remove the tumour (figs 3 and 4). Eur Respir J 2005; 26: 740-743

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“…The relative risks vary dramatically by site: from 852 for desmoid fibromas to 4.46 for pancreatic carcinomas (Giardiello et al 1993;Gurbuz et al 1994). Multiplicity of colorectal polyps and incidence of extracolonic manifestations are at least partially affected by the particular APC germline mutation (Enomoto et al 2000;Bertario et al 2001Bertario et al , 2003: mutations in the 59 end of the gene result in an attenuated form of FAP that is characterized by the development of few colonic polyps, while mutations in the 39 end increase the tendency to develop desmoid fibromas. Apc has been linked to several different biological processes through its interactions with other proteins.…”

Section: H Ighly Penetrant Familial Cancers Including 200mentioning

confidence: 99%

The Pleiotropic Phenotype of Apc Mutations in the Mouse: Allele Specificity and Effects of the Genetic Background

et al. 2008

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Familial adenomatous polyposis (FAP) is a human cancer syndrome characterized by the development of hundreds to thousands of colonic polyps and extracolonic lesions including desmoid fibromas, osteomas, epidermoid cysts, and congenital hypertrophy of the pigmented retinal epithelium. Afflicted individuals are heterozygous for mutations in the APC gene. Detailed investigations of mice heterozygous for mutations in the ortholog Apc have shown that other genetic factors strongly influence the phenotype. Here we report qualitative and quantitative modifications of the phenotype of Apc mutants as a function of three genetic variables: Apc allele, p53 allele, and genetic background. We have found major differences between the Apc alleles Min and 1638N in multiplicity and regionality of intestinal tumors, as well as in incidence of extracolonic lesions. By contrast, Min mice homozygous for either of two different knockout alleles of p53 show similar phenotypic effects. These studies illustrate the classic principle that functional genetics is enriched by assessing penetrance and expressivity with allelic series. The mouse permits study of an allelic gene series on multiple genetic backgrounds, thereby leading to a better understanding of gene action in a range of biological processes.

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Genotype and phenotype factors as determinants of desmoid tumors in patients with familial adenomatous polyposis

Cited by 206 publications

References 45 publications

Mutation spectrum of the APC gene in 83 Korean FAP families

Mutation spectrum of the APC gene in 83 Korean FAP families

A 20-year-old male with thoracic pain and a lower thoracic mass

The Pleiotropic Phenotype of Apc Mutations in the Mouse: Allele Specificity and Effects of the Genetic Background

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