Localization of the gene for Cowden disease to chromosome 10q22-23
Marcel R. Nelen,George W. Padberg,E. A. J. Peeters,Albert Y. Lin,B. Van Den Helm,Rune R. Frants,Valérie Coulon,Alisa M. Goldstein,M.M.M. van Reen,Douglas F. Easton,Rosalind A. Eeles,Shirley Hodgson,John J. Mulvihill,Victoria Murday,Monica Tucker,E.C.M. Mariman,T. M. Starink,Bruce Ponder,Hans-Hilger Ropers,Hannie Kremer,Michel Longy,Charis Eng,Charis Eng +22 more
TLDR
Cowden disease (CD) (MIM 158350), or multiple hamartoma syndrome, is a rare autosomal dominant familial cancer syndrome with a high risk of breast cancer and central nervous system manifestations of CD were emphasized only recently.Abstract:
Cowden disease (CD) (MIM 158350), or multiple hamartoma syndrome, is a rare autosomal dominant familial cancer syndrome with a high risk of breast cancer. Its clinical features include a wide array of abnormalities but the main characteristics are hamartomas of the skin, breast, thyroid, oral mucosa and intestinal epithelium. The pathognomonic hamartomatous features of CD include multiple smooth facial papules, acral keratosis and multiple oral papillomas. The pathological hallmark of the facial papules are multiple trichilemmomas. Expression of the disease is variable and penetrance of the dermatological lesions is assumed to be virtually complete by the age of twenty. Central nervous system manifestations of CD were emphasized only recently and include megalencephaly, epilepsy and dysplastic gangliocytomas of the cerebellum (Lhermitte-Duclos disease, LDD). Early diagnosis is important since female patients with CD are at risk of developing breast cancer. Other lesions include benign and malignant disease of the thyroid, intestinal polyps and genitourinary abnormalities. To localize the gene for CD, an autosomal genome scan was performed. A total of 12 families were examined, resulting in a maximum lod score of 8.92 at theta = 0.02 with the marker D10S573 located on chromosome 10q22-23.read more
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Identification of a candidate tumour suppressor gene, MMAC1 , at chromosome 10q23.3 that is mutated in multiple advanced cancers
Peter A. Steck,Mark A. Pershouse,Samar A. Jasser,W. K. A. Yung,Huai Lin,Azra H. Ligon,Lauren A. Langford,Michelle Baumgard,T. Hattier,Thaylon Davis,Cheryl Frye,Rong Hu,Bradley D. Swedlund,David H. F. Teng,Sean V. Tavtigian +14 more
TL;DR: The results identify a strong candidate tumour suppressor gene at chromosome 10q23.3, whose loss of function appears to be associated with the oncogenesis of multiple human cancers.
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Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome
Danny Liaw,Deborah J. Marsh,Jing Li,Patricia L. M. Dahia,Steven I. Wang,Z. Zheng,Shikha Bose,K. M. Call,Hui C. Tsou,Monica Peacocke,Charis Eng,Ramon Parsons +11 more
TL;DR: Mutational analysis of PTEN in CD kindreds has identified germline mutations that are predicted to disrupt the protein tyrosine/dual-specificity phosphatase domain of this gene, and implies that PTEN may play a role in organizing the relationship of different cell types within an organ during development.
Journal ArticleDOI
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.
Sapna Syngal,Randall E. Brand,James M. Church,Francis M. Giardiello,Heather Hampel,Randall W. Burt +5 more
TL;DR: Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers.
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The Biology and Clinical Relevance of the PTEN Tumor Suppressor Pathway
TL;DR: It is raised the possibility that drugs targeting these kinases, or PI3K itself, might have significant therapeutic activity in PTEN-null cancers and phase I and phase II trials of inhibitors of mTOR are underway.
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