title: PTEN hamartoma tumor syndromes.
abstract: The PTEN hamartoma tumor syndromes (PHTS) are a collection of rare clinical syndromes characterized by germline mutations of the tumor suppressor PTEN. These syndromes are driven by cellular overgrowth, leading to benign hamartomas in virtually any organ. Cowden syndrome (CS), the prototypic PHTS syndrome, is associated with increased susceptibility to breast, thyroid, and endometrial cancer. PTEN is located on chromosome 10q22-23 and negatively regulates the prosurvival PI3K/Akt/mTOR pathway through its lipid phosphatase activity. Loss of PTEN activates this pathway and leads to increased cellular growth, migration, proliferation, and survival. Clinical management of patients with PHTS, particularly those with CS, should include early and frequent screening, surveillance, and preventive care for associated malignancies. Concomitant with improved understanding of the biology of PTEN and the PI3K/Akt/mTOR pathway, inhibitors of this pathway are being developed as anticancer agents. These medications could have applications for patients with PHTS, for whom no medical options currently exist.
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Blumenthal
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Dennis
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006223:Hamartoma Syndrome, Multiple / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
chemical_list: D000970:Antineoplastic Agents; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C494929:PTEN protein, human
references.citation: JAMA. 2006 Jun 21;295(23):2727-41
references.pmid: 16754727
references.citation: Cell. 2007 Jan 12;128(1):157-70
references.pmid: 17218262
references.citation: Cancer Res. 2007 Sep 1;67(17):7960-5
references.pmid: 17804702
references.citation: Cell. 1998 Oct 2;95(1):29-39
references.pmid: 9778245
references.citation: Physiol Res. 2005;54(1):1-16
references.pmid: 15717836
references.citation: J Pediatr Surg. 1992 Jun;27(6):722-3
references.pmid: 1501032
references.citation: AJNR Am J Neuroradiol. 1992 Jan-Feb;13(1):287-90
references.pmid: 1595461
references.citation: J Med Genet. 2000 Nov;37(11):828-30
references.pmid: 11073535
references.citation: PLoS Med. 2008 Jan 22;5(1):e8
references.pmid: 18215105
references.citation: Cancer Res. 2008 Jan 15;68(2):425-33
references.pmid: 18199536
references.citation: J Med Genet. 2001 Mar;38(3):159-64
references.pmid: 11238682
references.citation: J Med Genet. 2002 Dec;39(12):937-40
references.pmid: 12471211
references.citation: Breast Dis. 2006-2007;27:21-50
references.pmid: 17917139
references.citation: J Med Genet. 2001 Dec;38(12):820-3
references.pmid: 11748304
references.citation: Eur J Dermatol. 2007 Mar-Apr;17(2):133-6
references.pmid: 17337396
references.citation: Am J Gastroenterol. 2003 Jun;98(6):1429-34
references.pmid: 12818292
references.citation: Oncogene. 2001 Jul 27;20(33):4457-65
references.pmid: 11494141
references.citation: Arch Pathol. 1971 Jul;92(1):1-5
references.pmid: 5091590
references.citation: Am J Med Genet. 1989 Dec;34(4):548-51
references.pmid: 2624267
references.citation: Lancet. 2001 Jul 21;358(9277):210-1
references.pmid: 11476841
references.citation: Circulation. 2000 Feb 15;101(6):660-7
references.pmid: 10673259
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10320-5
references.pmid: 11504907
references.citation: Am J Med Genet. 1984 Oct;19(2):225-34
references.pmid: 6507473
references.citation: J Med Genet. 2004 May;41(5):323-6
references.pmid: 15121767
references.citation: Cell. 2007 Jan 12;128(1):141-56
references.pmid: 17218261
references.citation: Am J Hum Genet. 2006 Jul;79(1):23-30
references.pmid: 16773562
references.citation: J Neuropathol Exp Neurol. 2005 Apr;64(4):341-9
references.pmid: 15835270
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10314-9
references.pmid: 11504908
references.citation: Cancer Res. 2005 Aug 15;65(16):7052-8
references.pmid: 16103051
references.citation: Nat Genet. 1997 May;16(1):64-7
references.pmid: 9140396
references.citation: Ann Intern Med. 1963 Jan;58:136-42
references.pmid: 13931122
references.citation: J Natl Cancer Inst. 2005 Nov 16;97(22):1652-62
references.pmid: 16288118
references.citation: Oncogene. 2007 Mar 22;26(13):1932-40
references.pmid: 17001314
references.citation: Lancet. 2001 Dec 15;358(9298):2079-80
references.pmid: 11755638
references.citation: J Med Genet. 2007 Sep;44(9):594-602
references.pmid: 17526801
references.citation: Eur J Hum Genet. 2007 Jul;15(7):767-73
references.pmid: 17392703
references.citation: Hum Mol Genet. 1999 Aug;8(8):1461-72
references.pmid: 10400993
references.citation: Nat Rev Cancer. 2007 Jan;7(1):35-45
references.pmid: 17167516
references.citation: Semin Oncol. 2007 Oct;34(5):428-34
references.pmid: 17920899
references.citation: Clin Cancer Res. 2002 Jun;8(6):1904-14
references.pmid: 12060635
references.citation: Exp Cell Res. 2001 Mar 10;264(1):29-41
references.pmid: 11237521
references.citation: Br J Dermatol. 2007 May;156(5):1089-90
references.pmid: 17388921
references.citation: Nat Genet. 1998 Aug;19(4):348-55
references.pmid: 9697695
references.citation: Endocr Relat Cancer. 2001 Sep;8(3):249-58
references.pmid: 11566616
references.citation: Ann Genet. 1996;39(1):35-42
references.pmid: 9297442
references.citation: Cell. 2007 Jan 12;128(1):129-39
references.pmid: 17218260
references.citation: Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12479-84
references.pmid: 9356475
references.citation: Am J Med Genet C Semin Med Genet. 2005 Aug 15;137C(1):38-52
references.pmid: 16010681
references.citation: Am J Med Genet A. 2004 Oct 1;130A(2):123-7
references.pmid: 15372512
references.citation: N Engl J Med. 2001 Jul 19;345(3):159-64
references.pmid: 11463009
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2007 Jun 5;144B(4):484-91
references.pmid: 17427195
references.citation: Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1563-8
references.pmid: 9990064
references.citation: Hum Mol Genet. 2006 Mar 1;15(5):777-87
references.pmid: 16436456
references.citation: Hum Mol Genet. 2001 Mar 15;10(6):605-16
references.pmid: 11230180
references.citation: Cancer Res. 2006 Feb 1;66(3):1500-8
references.pmid: 16452206
references.citation: J Natl Cancer Inst. 2001 Nov 7;93(21):1633-7
references.pmid: 11698567
references.citation: J Med Genet. 2007 Sep;44(9):579-85
references.pmid: 17526800
references.citation: J Med Genet. 2001 Jan;38(1):52-8
references.pmid: 11332402
references.citation: Nat Clin Pract Oncol. 2008 Jun;5(6):357-61
references.pmid: 18431376
references.citation: Science. 1998 Jun 5;280(5369):1614-7
references.pmid: 9616126
references.citation: Hum Pathol. 1998 Jan;29(1):47-53
references.pmid: 9445133
references.citation: Am J Med Genet A. 2003 Nov 1;122A(4):323-4
references.pmid: 14518070
references.citation: Cancer Res. 2002 Sep 1;62(17):5027-34
references.pmid: 12208757
references.citation: Cancer Res. 2006 Jul 1;66(13):6546-52
references.pmid: 16818626
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5703-8
references.pmid: 15824318
references.citation: Am J Hum Genet. 2003 Aug;73(2):404-11
references.pmid: 12844284
references.citation: Hum Mol Genet. 1998 Mar;7(3):507-15
references.pmid: 9467011
references.citation: Eur J Pediatr. 1983 Mar;140(1):5-12
references.pmid: 6873112
references.citation: Clin Genet. 1986 Mar;29(3):222-33
references.pmid: 3698331
references.citation: N Engl J Med. 2008 Jan 10;358(2):140-51
references.pmid: 18184959
references.citation: Ann Diagn Pathol. 1999 Dec;3(6):331-40
references.pmid: 10594284
references.citation: Hum Mutat. 2003 Sep;22(3):183-98
references.pmid: 12938083
references.citation: Am J Hum Genet. 2003 Nov;73(5):1191-8
references.pmid: 14566704
references.citation: Gut. 2008 May;57(5):623-7
references.pmid: 18178612
references.citation: Curr Biol. 1998 Oct 22;8(21):1169-78
references.pmid: 9799734
references.citation: JAMA. 2005 Nov 16;294(19):2465-73
references.pmid: 16287957