Hitting the Mark in Hamartoma Syndromes

Advances in Dermatology

Volumn 22, Issue , 2006, Pages 181-200

  Darling, Thomas N ^a  

^a Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CONGENITAL TUMOR; GENETICS; HUMAN; MUTATION; PATHOLOGY; PATHOPHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE;

GENES, TUMOR SUPPRESSOR; HAMARTOMA SYNDROME, MULTIPLE; HUMANS; MUTATION; SIGNAL TRANSDUCTION;

EID: 33845659663     PISSN: 08820880     EISSN: None     Source Type: Book Series    
DOI: 10.1016/j.yadr.2006.09.004     Document Type: Review

References (109)

1. Ober W.B. Selected items from the history of pathology. Eugen Albrecht, MD (1872-1908): hamartoma and choristoma. Am J Pathol 91 3 (1978) 606
2. Poomeechaiwong S., and Golitz L.E. Hamartomas. Adv Dermatol 5 (1990) 257-287 [discussion 288]
3. Weary P.E., Gorlin R.J., Gentry Jr. W.C., et al. Multiple hamartoma syndrome (Cowden's disease). Arch Dermatol 106 5 (1972) 682-690
4. Cooper J.R. Brain tumors in hereditary multiple system hamartomatosis (tuberous sclerosis). J Neurosurg 34 (1971) 194-202
5. Gomez M.R. The tuberous sclerosis complex, a prototype of hamartiosis and hamartomatosis. J Dermatol 19 11 (1992) 892-896
6. Willis R.A. The hamartomatous syndromes: their clinical, pathological and fundamental aspects. Med J Aust 310 (1965) 827-833
7. Schreibman I.R., Baker M., Amos C., et al. The hamartomatous polyposis syndromes: a clinical and molecular review. Am J Gastroenterol 100 2 (2005) 476-490
8. Sweet K., Willis J., Zhou X.P., et al. Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis. JAMA 294 19 (2005) 2465-2473
9. Lee D.A., Grossman M.E., Schneiderman P., et al. Genetics of skin appendage neoplasms and related syndromes. J Med Genet 42 11 (2005) 811-819
10. Reed R.J. Tricholemmoma. A cutaneous hamartoma. Am J Dermatopathol 2 3 (1980) 227-228
11. Reed R.J., and Ackerman A.B. Pathology of the adventitial dermis. Anatomic observations and biologic speculations. Hum Pathol 4 2 (1973) 207-217
12. Gottfried O.N., Viskochil D.H., Fults D.W., et al. Molecular, genetic, and cellular pathogenesis of neurofibromas and surgical implications. Neurosurgery 58 1 (2006) 1-16
13. Bauer A.J., and Stratakis C.A. The lentiginoses: cutaneous markers of systemic disease and a window to new aspects of tumourigenesis. J Med Genet 42 11 (2005) 801-810
14. Benjamin D.R. Cellular composition of the angiofibromas in tuberous sclerosis. Pediatr Pathol Lab Med 16 6 (1996) 893-899
15. Li S., Takeuchi F., Wang J.A., et al. MCP-1 overexpressed in tuberous sclerosis lesions acts as a paracrine factor for tumor development. J Exp Med 202 5 (2005) 617-624
16. Papakonstantinou E., Dionyssopoulos A., Pesintzaki C., et al. Expression of proteoglycans and glycosaminoglycans in angiofibroma and fibrous plaque skin lesions from patients with tuberous sclerosis. Arch Dermatol Res 295 4 (2003) 138-145
17. Liaw D., Marsh D.J., Li J., et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 16 1 (1997) 64-67
18. Marchuk D.A., Saulino A.M., Tavakkol R., et al. cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product. Genomics 11 4 (1991) 931-940
19. van Slegtenhorst M., de Hoogt R., Hermans C., et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 277 5327 (1997) 805-808
20. The European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 75 7 (1993) 1305-1315
21. Hemminki A., Markie D., Tomlinson I., et al. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 391 6663 (1998) 184-187
22. Pilarski R., and Eng C. Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome. J Med Genet 41 5 (2004) 323-326
23. Aretz S., Stienen D., Uhlhaas S., et al. High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. Hum Mutat 26 6 (2005) 513-519
24. Sancak O., Nellist M., Goedbloed M., et al. Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype-phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex. Eur J Hum Genet 13 6 (2005) 731-741
25. Eng C. PTEN: one gene, many syndromes. Hum Mutat 22 3 (2003) 183-198
26. Messiaen L.M., Callens T., Mortier G., et al. Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects. Hum Mutat 15 6 (2000) 541-555
27. Knudson Jr. A.G. Contribution and mechanisms of genetic predisposition to cancer: hereditary cancers and anti-oncogenes. Prog Clin Biol Res 132C (1983) 351-360
28. Knudson Jr. J.A.G. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68 4 (1971) 820-823
29. Miyaki M., Iijima T., Hosono K., et al. Somatic mutations of LKB1 and beta-catenin genes in gastrointestinal polyps from patients with Peutz-Jeghers syndrome. Cancer Res 60 22 (2000) 6311-6313
30. Wang Z.J., Ellis I., Zauber P., et al. Allelic imbalance at the LKB1 (STK11) locus in tumours from patients with Peutz-Jeghers' syndrome provides evidence for a hamartoma-(adenoma)-carcinoma sequence. J Pathol 188 1 (1999) 9-13
31. Marsh D.J., Dahia P.L., Coulon V., et al. Allelic imbalance, including deletion of PTEN/MMACI, at the Cowden disease locus on 10q22-23, in hamartomas from patients with Cowden syndrome and germline PTEN mutation. Genes Chromosomes Cancer 21 1 (1998) 61-69
32. Yu J., Astrinidis A., and Henske E.P. Chromosome 16 loss of heterozygosity in tuberous sclerosis and sporadic lymphangiomyomatosis. Am J Respir Crit Care Med 164 (2001) 1537-1540
33. Sepp T., Yates J.R., and Green A.J. Loss of heterozygosity in tuberous sclerosis hamartomas. J Med Genet 33 11 (1996) 962-964
34. Colman S.D., Williams C.A., and Wallace M.R. Benign neurofibromas in type 1 neurofibromatosis (NF1) show somatic deletions of the NF1 gene. Nat Genet 11 1 (1995) 90-92
35. Sawada S., Florell S., Purandare S.M., et al. Identification of NF1 mutations in both alleles of a dermal neurofibroma. Nat Genet 14 1 (1996) 110-112
36. Serra E., Puig S., Otero D., et al. Confirmation of a double-hit model for the NF1 gene in benign neurofibromas. Am J Hum Genet 61 3 (1997) 512-519
37. Henske E.P., Neumann H.P., Scheithauer B.W., et al. Loss of heterozygosity in the tuberous sclerosis (TSC2) region of chromosome band 16p13 occurs in sporadic as well as TSC-associated renal angiomyolipomas. Genes Chromosomes Cancer 13 4 (1995) 295-298
38. Henske E.P., Scheithauer B.W., Short M.P., et al. Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions. Am J Hum Genet 59 2 (1996) 400-406
39. Niida Y., Stemmer-Rachamimov A.O., Logrip M., et al. Survey of somatic mutations in tuberous sclerosis complex (TSC) hamartomas suggests different genetic mechanisms for pathogenesis of TSC lesions. Am J Hum Genet 69 3 (2001) 493-503
40. Au K.S., Hebert A.A., Roach E.S., et al. Complete inactivation of the TSC2 gene leads to formation of hamartomas. Am J Hum Genet 65 6 (1999) 1790-1795
41. Henske E.P., Wessner L.L., Golden J., et al. Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors. Am J Pathol 151 6 (1997) 1639-1647
42. Payne S.R., and Kemp C.J. Tumor suppressor genetics. Carcinogenesis 26 12 (2005) 2031-2045
43. Han S., Santos T.M., Puga A., et al. Phosphorylation of tuberin as a novel mechanism for somatic inactivation of the tuberous sclerosis complex proteins in brain lesions. Cancer Res 64 3 (2004) 812-816
44. Trojan J., Plotz G., Brieger A., et al. Activation of a cryptic splice site of PTEN and loss of heterozygosity in benign skin lesions in Cowden disease. J Invest Dermatol 117 6 (2001) 1650-1653
45. Green A.J., Sepp T., and Yates J.R. Clonality of tuberous sclerosis harmatomas shown by nonrandom X-chromosome inactivation. Hum Genet 97 2 (1996) 240-243
46. Miller S.J., Rangwala F., Williams J., et al. Large-scale molecular comparison of human Schwann cells to malignant peripheral nerve sheath tumor cell lines and tissues. Cancer Res 66 5 (2006) 2584-2591
47. Kluwe L., Friedrich R., and Mautner V.F. Loss of NF1 allele in Schwann cells but not in fibroblasts derived from an NF1-associated neurofibroma. Genes Chromosomes Cancer 24 3 (1999) 283-285
48. Rutkowski J.L., Wu K., Gutmann D.H., et al. Genetic and cellular defects contributing to benign tumor formation in neurofibromatosis type 1. Hum Mol Genet 9 7 (2000) 1059-1066
49. Fackler I., DeClue J.E., Rust H., et al. Loss of expression of tuberin and hamartin in tuberous sclerosis complex-associated but not in sporadic angiofibromas. J Cutan Pathol 30 3 (2003) 174-177
50. Nguyen-Vu P.A., Fackler I., Rust A., et al. Loss of tuberin, the tuberous-sclerosis-complex-2 gene product is associated with angiogenesis. J Cutan Pathol 28 9 (2001) 470-475
51. Darling T.N., Skarulis M.C., Steinberg S.M., et al. Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1. Arch Dermatol 133 7 (1997) 853-857
52. Dong Q., Debelenko L.V., Chandrasekharappa S.C., et al. Loss of heterozygosity at 11q13: analysis of pituitary tumors, lung carcinoids, lipomas, and other uncommon tumors in subjects with familial multiple endocrine neoplasia type 1. J Clin Endocrinol Metab 82 5 (1997) 1416-1420
53. Pack S., Turner M.L., Zhuang Z., et al. Cutaneous tumors in patients with multiple endocrine neoplasia type 1 show allelic deletion of the MEN1 gene. J Invest Dermatol 110 4 (1998) 438-440
54. Vortmeyer A.O., Boni R., Pack S.D., et al. Perivascular cells harboring multiple endocrine neoplasia type 1 alterations are neoplastic cells in angiofibromas. Cancer Res 59 2 (1999) 274-278
55. Kurtz A., Lueth M., Kluwe L., et al. Somatic mitochondrial DNA mutations in neurofibromatosis type 1-associated tumors. Mol Cancer Res 2 8 (2004) 433-441
56. Henske E.P. Metastasis of benign tumor cells in tuberous sclerosis complex. Genes Chromosomes Cancer 38 4 (2003) 376-381
57. Karbowniczek M., Astrinidis A., Balsara B.R., et al. Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism. Am J Respir Crit Care Med 167 7 (2003) 976-982
58. Crooks D.M., Pacheco-Rodriguez G., DeCastro R.M., et al. Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis. Proc Natl Acad Sci U S A 101 50 (2004) 17462-17467
59. Sansal I., and Sellers W.R. The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol 22 14 (2004) 2954-2963
60. Spicer J., and Ashworth A. LKB1 kinase: master and commander of metabolism and polarity. Curr Biol 14 10 (2004) R383-R385
61. Hardie D.G. New roles for the LKB1→AMPK pathway. Curr Opin Cell Biol 17 2 (2005) 167-173
62. Kwiatkowski D.J., and Manning B.D. Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways. Hum Mol Genet 14 (2005) R251-R258
63. Dan H.C., Sun M., Yang L., et al. Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin. J Biol Chem 277 38 (2002) 35364-35370
64. Inoki K., Li Y., Zhu T., et al. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signaling. Nat Cell Biol 4 9 (2002) 648-657
65. Potter C.J., Pedraza L.G., and Xu T. Akt regulates growth by directly phosphorylating Tsc2. Nat Cell Biol 4 9 (2002) 658-665
66. Johannessen C.M., Reczek E.E., James M.F., et al. The NF1 tumor suppressor critically regulates TSC2 and mTOR. Proc Natl Acad Sci U S A 102 24 (2005) 8573-8578
67. Ma L., Chen Z., Erdjument-Bromage H., et al. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 121 2 (2005) 179-193
68. Roux P.P., Ballif B.A., Anjum R., et al. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc Natl Acad Sci U S A 101 37 (2004) 13489-13494
69. Shaw R.J., Bardeesy N., Manning B.D., et al. The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell 6 1 (2004) 91-99
70. Corradetti M.N., Inoki K., Bardeesy N., et al. Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev 18 13 (2004) 1533-1538
71. Mehenni H., Lin-Marq N., Buchet-Poyau K., et al. LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes. Hum Mol Genet 14 15 (2005) 2209-2219
72. Hand J.L., and Rogers III R.S. Oral manifestations of genodermatoses. Dermatol Clin 21 1 (2003) 183-194
73. Lowe N.J. Peutz-Jeghers syndrome with pigmented oral papillomas. Arch Dermatol 111 4 (1975) 503-505
74. High W.A., Stewart D., Essary L.R., et al. Sclerotic fibroma-like change in various neoplastic and inflammatory skin lesions: is sclerotic fibroma a distinct entity?. J Cutan Pathol 31 5 (2004) 373-378
75. O'Shea W.F., and Powers J.E. Solitary retinal astrocytoma. J Am Optom Assoc 62 7 (1991) 519-524
76. Amer M., Mostafa F.F., and Nasr A.N. Lentiginous macules and patches of neurofibromatosis (an approach to better terminology). J Eur Acad Dermatol Venereol 15 1 (2001) 39-42
77. Ceylan C., Ozdemir F., Ozturk G., et al. Tuberous sclerosis associated with multiple speckled lentiginous nevi. J Eur Acad Dermatol Venereol 17 5 (2003) 616-617
78. Kim B.K., Kim Y.I., and Kim W.H. Hamartomatous gastric polyposis in a patient with tuberous sclerosis. J Korean Med Sci 15 4 (2000) 467-470
79. Devroede G., Lemieux B., Masse S., et al. Colonic hamartomas in tuberous sclerosis. Gastroenterology 94 1 (1988) 182-188
80. Kim H.R., and Kim Y.J. Neurofibromatosis of the colon and rectum combined with other manifestations of von Recklinghausen's disease: report of a case. Dis Colon Rectum 41 9 (1998) 1187-1192
81. Maertens O., Prenen H., Debiec-Rychter M., et al. Molecular pathogenesis of multiple gastrointestinal stromal tumors in NF1 patients. Hum Mol Genet 15 6 (2006) 1015-1023
82. Miettinen M., Fetsch J.F., Sobin L.H., et al. Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol 30 1 (2006) 90-96
83. Kousseff B.G. The phakomatoses as paracrine growth disorders (paracinopathies). Clin Genet 37 2 (1990) 97-105
84. Arbiser J.L., Brat D., Hunter S., et al. Tuberous sclerosis-associated lesions of the kidney, brain, and skin are angiogenic neoplasms. J Am Acad Dermatol 46 3 (2002) 376-380
85. Brugarolas J.B., Vazquez F., Reddy A., et al. TSC2 regulates VEGF through mTOR-dependent and -independent pathways. Cancer Cell 4 2 (2003) 147-158
86. El-Hashemite N., Walker V., Zhang H., et al. Loss of Tsc1 or Tsc2 induces vascular endothelial growth factor production through mammalian target of rapamycin. Cancer Res 63 17 (2003) 5173-5177
87. Hamada K., Sasaki T., Koni P.A., et al. The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis. Genes Dev 19 17 (2005) 2054-2065
88. Kotsuji-Maruyama T., Imakado S., Kawachi Y., et al. PDGF-BB induces MAP kinase phosphorylation and VEGF expression in neurofibroma-derived cultured cells from patients with neurofibromatosis 1. J Dermatol 29 11 (2002) 713-717
89. Kawachi Y., Xu X., Ichikawa E., et al. Expression of angiogenic factors in neurofibromas. Exp Dermatol 12 4 (2003) 412-417
90. Arbiser J.L., Flynn E., and Barnhill R.L. Analysis of vascularity of human neurofibromas. J Am Acad Dermatol 38 (1998) 950-954
91. Bardeesy N., Sinha M., Hezel A.F., et al. Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Nature 419 6903 (2002) 162-167
92. Ylikorkala A., Rossi D.J., Korsisaari N., et al. Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice. Science 293 5533 (2001) 1323-1326
93. Abraham R.T. mTOR as a positive regulator of tumor cell responses to hypoxia. Curr Top Microbiol Immunol 279 (2004) 299-319
94. Liu L., Cash T.P., Jones R.G., et al. Hypoxia-induced energy stress regulates mRNA translation and cell growth. Mol Cell 21 4 (2006) 521-531
95. Brugarolas J., Lei K., Hurley R.L., et al. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 18 23 (2004) 2893-2904
96. Brugarolas J., and Kaelin Jr. W.G. Dysregulation of HIF and VEGF is a unifying feature of the familial hamartoma syndromes. Cancer Cell 6 1 (2004) 7-10
97. Zhu Y., Ghosh P., Charnay P., et al. Neurofibromas in NF1: Schwann cell origin and role of tumor environment. Science 296 5569 (2002) 920-922
98. Yang F.C., Ingram D.A., Chen S., et al. Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/- mast cells. J Clin Invest 112 12 (2003) 1851-1861
99. Mantovani A., Schioppa T., Biswas S.K., et al. Tumor-associated macrophages and dendritic cells as prototypic type II polarized myeloid populations. Tumori 89 5 (2003) 459-468
100. McNeish I.A., Bell S.J., and Lemoine N.R. Gene therapy progress and prospects: cancer gene therapy using tumour suppressor genes. Gene Ther 11 6 (2004) 497-503
101. Davies M.A., Kim S.J., Parikh N.U., et al. Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells. Clin Cancer Res 8 6 (2002) 1904-1914
102. Thomas G.V. mTOR and cancer: reason for dancing at the crossroads?. Curr Opin Genet Dev 16 1 (2006) 78-84
103. Franz D.N., Leonard J., Tudor C., et al. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol 59 3 (2006) 490-498
104. Gemmill R.M., Zhou M., Costa L., et al. Synergistic growth inhibition by Iressa and Rapamycin is modulated by VHL mutations in renal cell carcinoma. Br J Cancer 92 12 (2005) 2266-2277
105. Gau C.L., Kato-Stankiewicz J., Jiang C., et al. Farnesyltransferase inhibitors reverse altered growth and distribution of actin filaments in Tsc-deficient cells via inhibition of both rapamycin-sensitive and -insensitive pathways. Mol Cancer Ther 4 6 (2005) 918-926
106. Widemann B.C., Salzer W.L., Arceci R.J., et al. Phase I trial and pharmacokinetic study of the farnesyltransferase inhibitor tipifarnib in children with refractory solid tumors or neurofibromatosis type I and plexiform neurofibromas. J Clin Oncol 24 3 (2006) 507-516
107. Shaw R.J., Lamia K.A., Vasquez D., et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310 5754 (2005) 1642-1646
108. Gupta A., Cohen B.H., Ruggieri P., et al. Phase I study of thalidomide for the treatment of plexiform neurofibroma in neurofibromatosis 1. Neurology 60 1 (2003) 130-132
109. Moses M.A., Harper J., and Folkman J. Doxycycline treatment for lymphangioleiomyomatosis with urinary monitoring for MMPs. N Engl J Med 354 24 (2006) 2621-2622