Germline PTEN Mutations Are Rare and Highly Penetrant

Overview

Journal Hered Cancer Clin Pract

Publisher Biomed Central

Specialty Oncology

Date 2010 Mar 13

PMID 20223021

Citations 8

Authors

Cecilie F Rustad

Merete Bjornslett

Ketil R Heimdal

Lovise Maehle

Jaran Apold

Pal Moller

Affiliations

Soon will be listed here.

Abstract

Cowden syndrome (multiple hamartoma syndrome, MIM 158350) is an early onset syndrome characterized by multiple hamartomas in the skin, mucous membranes, breast, thyroid and endometrium. Patients with Cowden syndrome have increased risk of breast cancer, thyroid cancer and endometrial cancer. In 1997 germline mutations in PTEN were demonstrated to cause Cowden syndrome. We report the results of diagnostic and predictive testing in all families with Cowden syndrome or suspected Cowden syndrome registered at the Norwegian cancer family clinics. PTEN mutations were found in all six families meeting the clinical criteria for Cowden syndrome, in none of the two families assumed to have Cowden syndrome but not fulfilling the criteria, and in none of the eight families selected in our computerized medical files to have a combination of breast and thyroid cancers. Age-related penetrances for the various neoplasms are given. All families but one were small and de novo mutations were found.

Citing Articles

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PTEN, Longevity and Age-Related Diseases.

Tait I, Li Y, Lu J Biomedicines. 2017; 1(1):17-48.

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References

Marsh D, Kum J, Lunetta K, Bennett M, GORLIN R, Ahmed S . PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome. Hum Mol Genet. 1999; 8(8):1461-72. DOI: 10.1093/hmg/8.8.1461. View

Eng C . Genetics of Cowden syndrome: through the looking glass of oncology. Int J Oncol. 1998; 12(3):701-10. DOI: 10.3892/ijo.12.3.701. View

Starink T, van der Veen J, Arwert F, de Waal L, de Lange G, Gille J . The Cowden syndrome: a clinical and genetic study in 21 patients. Clin Genet. 1986; 29(3):222-33. DOI: 10.1111/j.1399-0004.1986.tb00816.x. View

Merg A, Howe J . Genetic conditions associated with intestinal juvenile polyps. Am J Med Genet C Semin Med Genet. 2004; 129C(1):44-55. DOI: 10.1002/ajmg.c.30020. View

Nelen M, van Staveren W, Peeters E, Hassel M, GORLIN R, Hamm H . Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. Hum Mol Genet. 1997; 6(8):1383-7. DOI: 10.1093/hmg/6.8.1383. View

Liaw D, Marsh D, Li J, Dahia P, Wang S, Zheng Z . Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet. 1997; 16(1):64-7. DOI: 10.1038/ng0597-64. View

Nelen M, Kremer H, Konings I, Schoute F, van Essen A, Koch R . Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations. Eur J Hum Genet. 1999; 7(3):267-73. DOI: 10.1038/sj.ejhg.5200289. View

Fitzgerald M, Marsh D, Wahrer D, Bell D, Caron S, Shannon K . Germline mutations in PTEN are an infrequent cause of genetic predisposition to breast cancer. Oncogene. 1998; 17(6):727-31. DOI: 10.1038/sj.onc.1201984. View

Lynch E, Ostermeyer E, Lee M, Arena J, Ji H, Dann J . Inherited mutations in PTEN that are associated with breast cancer, cowden disease, and juvenile polyposis. Am J Hum Genet. 1997; 61(6):1254-60. PMC: 1716102. DOI: 10.1086/301639. View

10.

Lynch H, de la Chapelle A . Hereditary colorectal cancer. N Engl J Med. 2003; 348(10):919-32. DOI: 10.1056/NEJMra012242. View

11.

Harada N, Sugimura T, Yoshimura R, Motomura S, Shirahama S, Naramoto J . Novel germline mutation of the PTEN gene in a Japanese family with Cowden disease. J Gastroenterol. 2003; 38(1):87-91. DOI: 10.1007/s005350300012. View

12.

Hanssen A, Fryns J . Cowden syndrome. J Med Genet. 1995; 32(2):117-9. PMC: 1050232. DOI: 10.1136/jmg.32.2.117. View

13.

Biesecker L, Rosenberg M, Vacha S, Turner J, COHEN M . PTEN mutations and proteus syndrome. Lancet. 2002; 358(9298):2079-80. DOI: 10.1016/S0140-6736(01)07109-4. View

14.

Smith J, Kirk E, Theodosopoulos G, Marshall G, Walker J, Rogers M . Germline mutation of the tumour suppressor PTEN in Proteus syndrome. J Med Genet. 2002; 39(12):937-40. PMC: 1757209. DOI: 10.1136/jmg.39.12.937. View

15.

LLOYD 2nd K, Dennis M . Cowden's disease. A possible new symptom complex with multiple system involvement. Ann Intern Med. 1963; 58:136-42. DOI: 10.7326/0003-4819-58-1-136. View

16.

Moller P, Evans G, Haites N, Vasen H, Reis M, Anderson E . Guidelines for follow-up of women at high risk for inherited breast cancer: consensus statement from the Biomed 2 Demonstration Programme on Inherited Breast Cancer. Dis Markers. 1999; 15(1-3):207-11. PMC: 3850824. DOI: 10.1155/1999/920109. View

17.

Eng C . Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Genet. 2000; 37(11):828-30. PMC: 1734465. DOI: 10.1136/jmg.37.11.828. View

18.

Marsh D, Dahia P, Caron S, Kum J, Frayling I, Tomlinson I . Germline PTEN mutations in Cowden syndrome-like families. J Med Genet. 1998; 35(11):881-5. PMC: 1051477. DOI: 10.1136/jmg.35.11.881. View

19.

Eng C . Cowden Syndrome. J Genet Couns. 2015; 6(2):181-92. DOI: 10.1023/A:1025664119494. View

20.

Cohen Jr M, Turner J, Biesecker L . Proteus syndrome: misdiagnosis with PTEN mutations. Am J Med Genet A. 2003; 122A(4):323-4. DOI: 10.1002/ajmg.a.20474. View