Hereditary desmoid disease.

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Hereditary desmoid disease.

Written	2006-08	Rodney J Scott
		School of Biomedical Sciences, Faculty of Health, University of Newcastle, Australia

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Identity

Other names Familial infiltrative fibromatosis.
Atlas_Id 10119

Genes implicated in APC CTNNB1
Inheritance Autosomal dominant disorder; frequency is less than 1/10⁵ newborns; unknown new mutation rate; variable disease expression; penetrance is unknown. Hereditary desmoid disease occurs primarily in association with familial adenomatous polyposis.

Clinics

Phenotype and clinics Normally, presence of multiple desmoid tumours especially in the mesentery. Desmoid tumours can develop elsewhere and are often initiated after trauma. Micro-adenomas in the lower gastrointestinal tract, often not reported. Upper GI polyps are often observed.

Neoplastic risk Strictly speaking desmoid tumours are not neoplastic but they are locally invasive and highly destructive. Often associated with extreme pain and respond poorly to treatment. Usually they occur in association with familial adenomatous polyposis. Desmoid tumours usually occur in the abdominal cavity and have been associated with traumatic events that include surgery and childbirth. They have been reported at other anatomical sites.

Treatment There is no defined treatment that is affective in all cases. Nevertheless, the use of non-steroidal anti-inflammatory drugs (NSAIDs) in combination with tamoxifen has been suggested but there is no firm evidence to indicate its benefit.

Evolution Disease development involves the loss of APC and appears to be associated with 3' APC germline mutations. Little is known about downstream events in the evolution of the disease.

Prognosis Patients with hereditary desmoid disease fall into three categories; those that develop disease, which spontaneously regresses (very rarely reported); patients with stabile disease that does not progress: and patients with severe progressive and fatal disease.

Genes involved and Proteins

Gene Name APC (Adenomatous Polyposis Coli)

Alias Deleted in polyposis 2.5 (DP2.5)

Location 5q21-q22

Protein
Description Tumour suppressor gene with multiple functions; Normal APC gene product interacts with adherens junction proteins a-catenin and b-catenin.

Expression APC expression is present in all cells but at varying levels.

Localisation Mainly in the cytoplasm but there is a nuclear localization signal and it is observed in the nucleus.

Function Primary function appears to be the regulation of b-catenin in association with GSK-b via the ubiquitin degradation pathway. It has also been shown to help orientate the mitotic spindle during cell replication.

Homology Partial homology with , where it is about 76% homologous in the first half of the protein.

Mutations
Germinal Many mutations have been described in the APC gene, most of which result in premature termination codons. With respect to familial desmoid disease two sites have been described that occur in the sparsely mutated 3'- region of the gene. Germline mutations at codon 1924 and 1860 have been reported in rare families with desmoid disease.

Somatic There appears to be a mutation cluster region in the APC gene that is centered around codon 1309. These mutations have only been described in colorectal tumours and there is little information with respect to desmoid disease.

Bibliography

Hereditary desmoid disease due to a frameshift mutation at codon 1924 of the APC gene.

Eccles DM, van der Luijt R, Breukel C, Bullman H, Bunyan D, Fisher A, Barber J, du Boulay C, Primrose J, Burn J, Fodde R

American journal of human genetics. 1996 ; 59 (6) : 1193-1201.

PMID 8940264

Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.

Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B, Clevers H

Science (New York, N.Y.). 1997 ; 275 (5307) : 1784-1787.

PMID 9065401

Desmoid tumour: a pleomorphic lesion.

Kulaylat MN, Karakousis CP, Keaney CM, McCorvey D, Bem J, Ambrus Sr JL

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 1999 ; 25 (5) : 487-497.

PMID 10527597

Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene.

Miyoshi Y, Nagase H, Ando H, Horii A, Ichii S, Nakatsuru S, Aoki T, Miki Y, Mori T, Nakamura Y

Human molecular genetics. 1992 ; 1 (4) : 229-233.

PMID 1338904

Familial infiltrative fibromatosis (desmoid tumours) (MIM135290) caused by a recurrent 3' APC gene mutation.

Scott RJ, Froggatt NJ, Trembath RC, Evans DG, Hodgson SV, Maher ER

Human molecular genetics. 1996 ; 5 (12) : 1921-1924.

PMID 8968744

Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome.

Yamashita YM, Jones DL, Fuller MT

Science (New York, N.Y.). 2003 ; 301 (5639) : 1547-1550.

PMID 12970569

Citation

This paper should be referenced as such :

Scott, JR

Hereditary desmoid disease

Atlas Genet Cytogenet Oncol Haematol. 2007;11(1):57-58.

Free journal version : [ pdf ] [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Tumors/HereditDesmoidID10119.html

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Other names	Familial infiltrative fibromatosis.
Atlas_Id	10119
Genes implicated in	APC CTNNB1
Inheritance	Autosomal dominant disorder; frequency is less than 1/10⁵ newborns; unknown new mutation rate; variable disease expression; penetrance is unknown. Hereditary desmoid disease occurs primarily in association with familial adenomatous polyposis.

Phenotype and clinics	Normally, presence of multiple desmoid tumours especially in the mesentery. Desmoid tumours can develop elsewhere and are often initiated after trauma. Micro-adenomas in the lower gastrointestinal tract, often not reported. Upper GI polyps are often observed.


Neoplastic risk	Strictly speaking desmoid tumours are not neoplastic but they are locally invasive and highly destructive. Often associated with extreme pain and respond poorly to treatment. Usually they occur in association with familial adenomatous polyposis. Desmoid tumours usually occur in the abdominal cavity and have been associated with traumatic events that include surgery and childbirth. They have been reported at other anatomical sites.
Treatment	There is no defined treatment that is affective in all cases. Nevertheless, the use of non-steroidal anti-inflammatory drugs (NSAIDs) in combination with tamoxifen has been suggested but there is no firm evidence to indicate its benefit.
Evolution	Disease development involves the loss of APC and appears to be associated with 3' APC germline mutations. Little is known about downstream events in the evolution of the disease.
Prognosis	Patients with hereditary desmoid disease fall into three categories; those that develop disease, which spontaneously regresses (very rarely reported); patients with stabile disease that does not progress: and patients with severe progressive and fatal disease.

Gene Name	APC (Adenomatous Polyposis Coli)
Alias	Deleted in polyposis 2.5 (DP2.5)
Location	5q21-q22

Protein
Description	Tumour suppressor gene with multiple functions; Normal APC gene product interacts with adherens junction proteins a-catenin and b-catenin.
Expression	APC expression is present in all cells but at varying levels.
Localisation	Mainly in the cytoplasm but there is a nuclear localization signal and it is observed in the nucleus.
Function	Primary function appears to be the regulation of b-catenin in association with GSK-b via the ubiquitin degradation pathway. It has also been shown to help orientate the mitotic spindle during cell replication.
Homology	Partial homology with , where it is about 76% homologous in the first half of the protein.

Mutations
Germinal	Many mutations have been described in the APC gene, most of which result in premature termination codons. With respect to familial desmoid disease two sites have been described that occur in the sparsely mutated 3'- region of the gene. Germline mutations at codon 1924 and 1860 have been reported in rare families with desmoid disease.
Somatic	There appears to be a mutation cluster region in the APC gene that is centered around codon 1309. These mutations have only been described in colorectal tumours and there is little information with respect to desmoid disease.

REVIEW articles	automatic search in PubMed
Last year articles	automatic search in PubMed