A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension

Cancer Treatment Reviews

Volumn 38, Issue 6, 2012, Pages 726-736

  Cavuoto, Paul ^a   Fenech, Michael F ^a  

^a CSIRO   (Australia)

Author keywords

Cancer growth control; Life span extension; Methionine; MTAP; Nutrition

Indexed keywords

5' METHYLTHIOADENOSINE PHOSPHORYLASE; ADENINE DERIVATIVE; FLUOROURACIL; FOLIC ACID; FOLINIC ACID; METHIONINE; METHIONINE GAMMA LYASE; OXALIPLATIN; POLYAMINE;

CANCER CELL; CANCER INHIBITION; CELL PROLIFERATION; CELL SURVIVAL; COLORECTAL CANCER; DIET RESTRICTION; DIET THERAPY; DNA METHYLATION; DNA POLYMORPHISM; FOLATE METABOLISM; GENE DELETION; GENE EXPRESSION; HUMAN; LIFESPAN; METHIONINE RESTRICTION; NONHUMAN; NUCLEOTIDE SEQUENCE; NUTRITIONAL VALUE; PROTEIN SYNTHESIS; REVIEW;

ANIMALS; CARBON-SULFUR LYASES; DIET; FOLIC ACID; HUMANS; LIFE EXPECTANCY; METHIONINE; NEOPLASMS; PHENOTYPE; PURINE-NUCLEOSIDE PHOSPHORYLASE;

EID: 84861701419     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2012.01.004     Document Type: Review

References (119)

1. Stratton M.R., Campbell P.J., Futreal P.A. The cancer genome. Nature 2009, 458:719-724.
2. World Cancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity and the prevention of cancer: a global perspective, 2007. Available from: http://www.dietandcancerreport.org.
3. Cellarier E., Durando X., Vasson M.P., et al. Methionine dependency and cancer treatment. Cancer Treat Rev 2003, 29:489-499.
4. Zimmerman J.A., Malloy V., Krajcik R., Orentreich N. Nutritional control of aging. Exp Gerontol 2003, 38:47-52.
5. Finkelstein J.D. Methionine metabolism in mammals. J Nutr Biochem 1990, 1:228-237.
6. Bolander-Gouaille C., Bottiglieri T. Homocysteine: related vitamins and neuropsychiatric disorders 2007, Springer-Verlag, Paris. 2nd ed.
7. Zingg J.M., Jones P.A. Genetic and epigenetic aspects of DNA methylation on genome expression, evolution, mutation and carcinogenesis. Carcinogenesis 1997, 18:869-882.
8. Sunden S.L., Renduchintala M.S., Park E.I., Miklasz S.D., Garrow T.A. Betaine-homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene. Arch Biochem Biophys 1997, 345:171-174.
9. Anderson M.E. Glutathione: an overview of biosynthesis and modulation. Chem Biol Interact 1998, 111-112:1-14.
10. Thomas T., Thomas T.J. Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications. Cell Mol Life Sci 2001, 58:244-258.
11. Pirkov I., Norbeck J., Gustafsson L., Albers E. A complete inventory of all enzymes in the eukaryotic methionine salvage pathway. FEBS J 2008, 275:4111-4120.
12. Quash G., Roch A.M., Chantepie J., et al. Methional derived from 4-methylthio-2-oxobutanoate is a cellular mediator of apoptosis in BAF3 lymphoid cells. Biochem J 1995, 305(Pt. 3):1017-1025.
13. Sugimura T., Birnbaum S.M., Winitz M., Greenstein J.P. Quantitative nutritional studies with water-soluble, chemically defined diets: VIII. The forced feeding of diets each lacking in one essential amino acid. Arch Biochem Biophys 1959, 81:448-455.
14. Buch L., Streeter D., Halpern R.M., et al. Inhibition of transfer ribonucleic acid methylase activity from several human tumors by nicotinamide and nicotinamide analogs. Biochemistry 1972, 11:393-397.
15. Halpern B.C., Clark B.R., Hardy D.N., Halpern R.M., Smith R.A. The effect of replacement of methionine by homocystine on survival of malignant and normal adult mammalian cells in culture. Proc Natl Acad Sci USA 1974, 71:1133-1136.
16. Breillout F., Antoine E., Poupon M.F. Methionine dependency of malignant tumors: a possible approach for therapy. J Natl Cancer Inst 1990, 82:1628-1632.
17. Hoffman R.M. Altered methionine metabolism, DNA methylation and oncogene expression in carcinogenesis. A review and synthesis. Biochim Biophys Acta 1984, 738:49-87.
18. Lu S., Epner D.E. Molecular mechanisms of cell cycle block by methionine restriction in human prostate cancer cells. Nutr Cancer 2000, 38:123-130.
19. Poirson-Bichat F., Goncalves R.A., Miccoli L., Dutrillaux B., Poupon M.F. Methionine depletion enhances the antitumoral efficacy of cytotoxic agents in drug-resistant human tumor xenografts. Clin Cancer Res 2000, 6:643-653.
20. Guo H.Y., Herrera H., Groce A., Hoffman R.M. Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture. Cancer Res 1993, 53:2479-2483.
21. Hoffman R.M., Erbe R.W. High in vivo rates of methionine biosynthesis in transformed human and malignant rat cells auxotrophic for methionine. Proc Natl Acad Sci USA 1976, 73:1523-1527.
22. Hoffman R.M., Jacobsen S.J., Erbe R.W. Reversion to methionine independence by malignant rat and SV40-transformed human fibroblasts. Biochem Biophys Res Commun 1978, 82:228-234.
23. Hoffman R.M., Jacobsen S.J., Erbe R.W. Reversion to methionine independence in simian virus 40-transformed human and malignant rat fibroblasts is associated with altered ploidy and altered properties of transformation. Proc Natl Acad Sci USA 1979, 76:1313-1317.
24. Coalson D.W., Mecham J.O., Stern P.H., Hoffman R.M. Reduced availability of endogenously synthesized methionine for S-adenosylmethionine formation in methionine-dependent cancer cells. Proc Natl Acad Sci USA 1982, 79:4248-4251.
25. Stern P.H., Mecham J.O., Wallace C.D., Hoffman R.M. Reduced free-methionine in methionine-dependent SV40-transformed human fibroblasts synthesizing apparently normal amounts of methionine. J Cell Physiol 1983, 117:9-14.
26. Behrmann I., Wallner S., Komyod W., et al. Characterization of methylthioadenosine phosphorylase (MTAP) expression in malignant melanoma. Am J Pathol 2003, 163:683-690.
27. Garcia-Castellano J.M., Villanueva A., Healey J.H., et al. Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma. Clin Cancer Res 2002, 8:782-787.
28. Komatsu A., Nagasaki K., Fujimori M., Amano J., Miki Y. Identification of novel deletion polymorphisms in breast cancer. Int J Oncol 2008, 33:261-270.
29. M'Soka T.J., Nishioka J., Taga A., et al. Detection of methylthioadenosine phosphorylase (MTAP) and p16 gene deletion in T cell acute lymphoblastic leukemia by real-time quantitative PCR assay. Leukemia 2000, 14:935-940.
30. Nobori T., Karras J.G., Della Ragione F., et al. Absence of methylthioadenosine phosphorylase in human gliomas. Cancer Res 1991, 51:3193-3197.
31. Schmid M., Malicki D., Nobori T., et al. Homozygous deletions of methylthioadenosine phosphorylase (MTAP) are more frequent than p16INK4A (CDKN2) homozygous deletions in primary non-small cell lung cancers (NSCLC). Oncogene 1998, 17:2669-2675.
32. Nobori T., Miura K., Wu D.J., et al. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 1994, 368:753-756.
33. Nobori T., Takabayashi K., Tran P., et al. Genomic cloning of methylthioadenosine phosphorylase: a purine metabolic enzyme deficient in multiple different cancers. Proc Natl Acad Sci USA 1996, 93:6203-6208.
34. Brat D.J., James C.D., Jedlicka A.E., et al. Molecular genetic alterations in radiation-induced astrocytomas. Am J Pathol 1999, 154:1431-1438.
35. Christopher S.A., Diegelman P., Porter C.W., Kruger W.D. Methylthioadenosine phosphorylase, a gene frequently codeleted with p16(cdkN2a/ARF), acts as a tumor suppressor in a breast cancer cell line. Cancer Res 2002, 62:6639-6644.
36. Tang B., Li Y.N., Kruger W.D. Defects in methylthioadenosine phosphorylase are associated with but not responsible for methionine-dependent tumor cell growth. Cancer Res 2000, 60:5543-5547.
37. Lubin M., Lubin A. Selective killing of tumors deficient in methylthioadenosine phosphorylase: a novel strategy. PLoS One 2009, 4:e5735.
38. Kindler H.L., Burris H.A., Sandler A.B., Oliff I.A. A phase II multicenter study of l-alanosine, a potent inhibitor of adenine biosynthesis, in patients with MTAP-deficient cancer. Invest New Drugs 2009, 27:75-81.
39. Basu I., Locker J., Cassera M.B., et al. Growth and metastases of human lung cancer are inhibited in mouse xenografts by a transition state analogue of 5'-methylthioadenosine phosphorylase. J Biol Chem 2010, 286:4902-4911.
40. Subhi A.L., Diegelman P., Porter C.W., et al. Methylthioadenosine phosphorylase regulates ornithine decarboxylase by production of downstream metabolites. J Biol Chem 2003, 278:49868-49873.
41. Kenyon S.H., Waterfield C.J., Timbrell J.A., Nicolaou A. Methionine synthase activity and sulphur amino acid levels in the rat liver tumour cells HTC and Phi-1. Biochem Pharmacol 2002, 63:381-391.
42. Stern P.H., Wallace C.D., Hoffman R.M. Altered methionine metabolism occurs in all members of a set of diverse human tumor cell lines. J Cell Physiol 1984, 119:29-34.
43. Drennan C.L., Huang S., Drummond J.T., Matthews R.G., Lidwig M.L. How a protein binds B12: a 3.0A X-ray structure of B12-binding domains of methionine synthase. Science 1994, 266:1669-1674.
44. Beetstra S., Suthers G., Dhillon V., et al. Methionine-dependence phenotype in the de novo pathway in BRCA1 and BRCA2 mutation carriers with and without breast cancer. Cancer Epidemiol Biomarkers Prev 2008, 17:2565-2571.
45. Tisdale M.J. Methionine metabolism in Walker carcinosarcoma in vitro. Eur J Cancer 1980, 16:407-414.
46. Kimura M., Umegaki K., Higuchi M., Thomas P., Fenech M. Methylenetetrahydrofolate reductase C677T polymorphism, folic acid and riboflavin are important determinants of genome stability in cultured human lymphocytes. J Nutr 2004, 134:48-56.
47. McNulty H., Dowey le R.C., Strain J.J., et al. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C→T polymorphism. Circulation 2006, 113:74-80.
48. Fiskerstrand T., Christensen B., Tysnes O.B., Ueland P.M., Refsum H. Development and reversion of methionine dependence in a human glioma cell line: relation to homocysteine remethylation and cobalamin status. Cancer Res 1994, 54:4899-4906.
49. Liteplo R.G., Hipwell S.E., Rosenblatt D.S., Sillaots S., Lue-Shing H. Changes in cobalamin metabolism are associated with the altered methionine auxotrophy of highly growth autonomous human melanoma cells. J Cell Physiol 1991, 149:332-338.
50. Loewy A.D., Niles K.M., Anastasio N., et al. Epigenetic modification of the gene for the vitamin B(12) chaperone MMACHC can result in increased tumorigenicity and methionine dependence. Mol Genet Metab 2009, 96:261-267.
51. Watkins D. Cobalamin metabolism in methionine-dependent human tumour and leukemia cell lines. Clin Invest Med 1998, 21:151-158.
52. Ma E., Iwasaki M., Junko I., et al. Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Brazilian women. BMC Cancer 2009, 9:122.
53. Lu M., Wang F., Qiu J. Methionine synthase A2756G polymorphism and breast cancer risk: a meta-analysis involving 18,953 subjects. Breast Cancer Res Treat 2010, 123:213-217.
54. Sharp L., Little J. Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol 2004, 159:423-443.
55. Linnebank M., Fliessbach K., Kolsch H., Rietschel M., Wullner U. The methionine synthase polymorphism c.2756A right curved arrow G (D919G) is relevant for disease-free longevity. Int J Mol Med 2005, 16:759-761.
56. Dhillon V., Thomas P., Fenech M. Effect of common polymorphisms in folate uptake and metabolism genes on frequency of micronucleated lymphocytes in a South Australian cohort. Mutat Res 2009, 665:1-6.
57. Bergstrom M., Ericson K., Hagenfeldt L., et al. PET study of methionine accumulation in glioma and normal brain tissue: competition with branched chain amino acids. J Comput Assist Tomogr 1987, 11:208-213.
58. Stern P.H., Hoffman R.M. Elevated overall rates of transmethylation in cell lines from diverse human tumors. In Vitro 1984, 20:663-670.
59. Judde J.G., Ellis M., Frost P. Biochemical analysis of the role of transmethylation in the methionine dependence of tumor cells. Cancer Res 1989, 49:4859-4865.
60. Hoshiya Y., Guo H., Kubota T., et al. Human tumors are methionine dependent in vivo. Anticancer Res 1995, 15:717-718.
61. Tang B., Mustafa A., Gupta S., et al. Methionine-deficient diet induces post-transcriptional downregulation of cystathionine beta-synthase. Nutrition 2009, 26:1170-1175.
62. Epner D.E., Morrow S., Wilcox M., Houghton J.L. Nutrient intake and nutritional indexes in adults with metastatic cancer on a phase I clinical trial of dietary methionine restriction. Nutr Cancer 2002, 42:158-166.
63. Breillout F., Hadida F., Echinard-Garin P., Lascaux V., Poupon M.F. Decreased rat rhabdomyosarcoma pulmonary metastases in response to a low methionine diet. Anticancer Res 1987, 7:861-867.
64. Guo H., Lishko V.K., Herrera H., et al. Therapeutic tumor-specific cell cycle block induced by methionine starvation in vivo. Cancer Res 1993, 53:5676-5679.
65. Komninou D., Leutzinger Y., Reddy B.S., Richie J.P. Methionine restriction inhibits colon carcinogenesis. Nutr Cancer 2006, 54:202-208.
66. Theuer R.C. Effect of essential amino acid restriction on the growth of female C57BL mice and their implanted BW10232 adenocarcinomas. J Nutr 1971, 101:223-232.
67. McCarty M.F., Barroso-Aranda J., Contreras F. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med Hypotheses 2009, 72:125-128.
68. Davey G.K., Spencer E.A., Appleby P.N., et al. EPIC-Oxford: lifestyle characteristics and nutrient intakes in a cohort of 33883 meat-eaters and 31546 non meat-eaters in the UK. Public Health Nutr 2003, 6:259-269.
69. Ornish D., Weidner G., Fair W.R., et al. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol 2005, 174:1065-1069. discussion 9-70.
70. Caro P., Gomez J., Sanchez I., et al. Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria. Rejuvenation Res 2009, 12:421-434.
71. Li Y., Liu L., Tollefsbol T.O. Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. FASEB J 2010, 24:1442-1453.
72. Fenech M.F. Nutriomes and nutrient arrays - the key to personalised nutrition for DNA damage prevention and cancer growth control. Genome Integr 2010, 1:11.
73. Orentreich N., Matias J.R., DeFelice A., Zimmerman J.A. Low methionine ingestion by rats extends life span. J Nutr 1993, 123:269-274.
74. Richie J.P., Leutzinger Y., Parthasarathy S., et al. Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J 1994, 8:1302-1307.
75. Miller R.A., Buehner G., Chang Y., et al. Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell 2005, 4:119-125.
76. Kreis W., Hession C. Isolation and purification of l-methionine-alpha-deamino-gamma-mercaptomethane-lyase (l-methioninase) from Clostridium sporogenes. Cancer Res 1973, 33:1862-1865.
77. Kreis W., Hession C. Biological effects of enzymatic deprivation of l-methionine in cell culture and an experimental tumor. Cancer Res 1973, 33:1866-1869.
78. Esaki N., Soda K. l-Methionine gamma-lyase from Pseudomonas putida and Aeromonas. Methods Enzymol 1987, 143:459-465.
79. Tan Y., Xu M., Guo H., et al. Anticancer efficacy of methioninase in vivo. Anticancer Res 1996, 16:3931-3936.
80. Tan Y., Xu M., Tan X., et al. Overexpression and large-scale production of recombinant l-methionine-alpha-deamino-gamma-mercaptomethane-lyase for novel anticancer therapy. Protein Expr Purif 1997, 9:233-245.
81. Sun X., Yang Z., Li S., et al. In vivo efficacy of recombinant methioninase is enhanced by the combination of polyethylene glycol conjugation and pyridoxal 5'-phosphate supplementation. Cancer Res 2003, 63:8377-8383.
82. Yang Z., Wang J., Yoshioka T., et al. Pharmacokinetics, methionine depletion, and antigenicity of recombinant methioninase in primates. Clin Cancer Res 2004, 10:2131-2138.
83. Tan Y., Xu M., Hoffman R.M. Broad selective efficacy of recombinant methioninase and polyethylene glycol-modified recombinant methioninase on cancer cells in vitro. Anticancer Res 2010, 30:1041-1046.
84. Hoffman R.M., Jacobsen S.J. Reversible growth arrest in simian virus 40-transformed human fibroblasts. Proc Natl Acad Sci USA 1980, 77:7306-7310.
85. Stern P.H., Hoffman R.M. Enhanced in vitro selective toxicity of chemotherapeutic agents for human cancer cells based on a metabolic defect. J Natl Cancer Inst 1986, 76:629-639.
86. Machover D., Zittoun J., Broet P., et al. Cytotoxic synergism of methioninase in combination with 5-fluorouracil and folinic acid. Biochem Pharmacol 2001, 61:867-876.
87. Goseki N., Endo M. Thiol depletion and chemosensitization on nimustine hydrochloride by methionine-depleting total parenteral nutrition. Tohoku J Exp Med 1990, 161:227-239.
88. Goseki N., Yamazaki S., Shimojyu K., et al. Synergistic effect of methionine-depleting total parenteral nutrition with 5-fluorouracil on human gastric cancer: a randomized, prospective clinical trial. Jpn J Cancer Res 1995, 86:484-489.
89. Durando X., Thivat E., Farges M.C., et al. Optimal methionine-free diet duration for nitrourea treatment: a phase I clinical trial. Nutr Cancer 2008, 60:23-30.
90. Durando X., Farges M.C., Buc E., et al. Dietary methionine restriction with FOLFOX regimen as first line therapy of metastatic colorectal cancer: a feasibility study. Oncology 2010, 78:205-209.
91. Goldberg R.M. Advances in the treatment of metastatic colorectal cancer. Oncologist 2005, 10(Suppl. 3):40-48.
92. Jagasia A.A., Block J.A., Qureshi A., et al. Chromosome 9 related aberrations and deletions of the CDKN2 and MTS2 putative tumor suppressor genes in human chondrosarcomas. Cancer Lett 1996, 105:91-103.
93. Jagasia A.A., Block J.A., Diaz M.O., et al. Partial deletions of the CDKN2 and MTS2 putative tumor suppressor genes in a myxoid chondrosarcoma. Cancer Lett 1996, 105:77-90.
94. Powell E.L., Leoni L.M., Canto M.I., et al. Concordant loss of MTAP and p16/CDKN2A expression in gastroesophageal carcinogenesis: evidence of homozygous deletion in esophageal noninvasive precursor lesions and therapeutic implications. Am J Surg Pathol 2005, 29:1497-1504.
95. Kim D.H., Muto M., Kuwahara Y., et al. Array-based comparative genomic hybridization of circulating esophageal tumor cells. Oncol Rep 2006, 16:1053-1059.
96. Kim J., Kim M.A., Min S.Y., et al. Downregulation of methylthioadenosine phosphorylase by homozygous deletion in gastric carcinoma. Genes Chromosomes Cancer 2011, 50:421-433.
97. Huang H.Y., Li S.H., Yu S.C., et al. Homozygous deletion of MTAP gene as a poor prognosticator in gastrointestinal stromal tumors. Clin Cancer Res 2009, 15:6963-6972.
98. Suzuki T., Maruno M., Wada K., et al. Genetic analysis of human glioblastomas using a genomic microarray system. Brain Tumor Pathol 2004, 21:27-34.
99. Zhang H., Chen Z.H., Savarese T.M. Codeletion of the genes for p16INK4, methylthioadenosine phosphorylase, interferon-alpha1, interferon-beta1, and other 9p21 markers in human malignant cell lines. Cancer Genet Cytogenet 1996, 86:22-28.
100. Perry A., Nobori T., Ru N., et al. Detection of p16 gene deletions in gliomas: a comparison of fluorescence in situ hybridization (FISH) versus quantitative PCR. J Neuropathol Exp Neurol 1997, 56:999-1008.
101. Olopade O.I., Jenkins R.B., Ransom D.T., et al. Molecular analysis of deletions of the short arm of chromosome 9 in human gliomas. Cancer Res 1992, 52:2523-2529.
102. Efferth T., Miyachi H., Drexler H.G., Gebhart E. Methylthioadenosine phosphorylase as target for chemoselective treatment of T-cell acute lymphoblastic leukemic cells. Blood Cells Mol Dis 2002, 28:47-56.
103. Bertin R., Acquaviva C., Mirebeau D., et al. CDKN2A, CDKN2B, and MTAP gene dosage permits precise characterization of mono- and bi-allelic 9p21 deletions in childhood acute lymphoblastic leukemia. Genes Chromosomes Cancer 2003, 37:44-57.
104. Kamath A., Tara H., Xiang B., et al. Double-minute MYC amplification and deletion of MTAP, CDKN2A, CDKN2B, and ELAVL2 in an acute myeloid leukemia characterized by oligonucleotide-array comparative genomic hybridization. Cancer Genet Cytogenet 2008, 183:117-120.
105. Usvasalo A., Ninomiya S., Raty R., et al. Focal 9p instability in hematologic neoplasias revealed by comparative genomic hybridization and single-nucleotide polymorphism microarray analyses. Genes Chromosomes Cancer 2010, 49:309-318.
106. Hori Y., Hori H., Yamada Y., et al. The methylthioadenosine phosphorylase gene is frequently co-deleted with the p16INK4a gene in acute type adult T-cell leukemia. Int J Cancer 1998, 75:51-56.
107. Mirebeau D., Acquaviva C., Suciu S., et al. The prognostic significance of CDKN2A, CDKN2B and MTAP inactivation in B-lineage acute lymphoblastic leukemia of childhood. Results of the EORTC studies 58881 and 58951. Haematologica 2006, 91:881-885.
108. Marce S., Balague O., Colomo L., et al. Lack of methylthioadenosine phosphorylase expression in mantle cell lymphoma is associated with shorter survival: implications for a potential targeted therapy. Clin Cancer Res 2006, 12:3754-3761.
109. Dreyling M.H., Roulston D., Bohlander S.K., Vardiman J., Olopade O.I. Codeletion of CDKN2 and MTAP genes in a subset of non-Hodgkin's lymphoma may be associated with histologic transformation from low-grade to diffuse large-cell lymphoma. Genes Chromosomes Cancer 1998, 22:72-78.
110. Krasinskas A.M., Bartlett D.L., Cieply K., Dacic S. CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival. Mod Pathol 2010, 23:531-538.
111. Illei P.B., Rusch V.W., Zakowski M.F., Ladanyi M. Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas. Clin Cancer Res 2003, 9:2108-2113.
112. Mora J., Alaminos M., de Torres C., et al. Comprehensive analysis of the 9p21 region in neuroblastoma suggests a role for genes mapping to 9p21-23 in the biology of favourable stage 4 tumours. Br J Cancer 2004, 91:1112-1118.
113. Brownhill S.C., Taylor C., Burchill S.A. Chromosome 9p21 gene copy number and prognostic significance of p16 in ESFT. Br J Cancer 2007, 96:1914-1923.
114. Hustinx S.R., Hruban R.H., Leoni L.M., et al. Homozygous deletion of the MTAP gene in invasive adenocarcinoma of the pancreas and in periampullary cancer: a potential new target for therapy. Cancer Biol Ther 2005, 4:83-86.
115. Hustinx S.R., Leoni L.M., Yeo C.J., et al. Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion. Mod Pathol 2005, 18:959-963.
116. Chen Z.H., Zhang H., Savarese T.M. Gene deletion chemoselectivity: codeletion of the genes for p16(INK4), methylthioadenosine phosphorylase, and the alpha- and beta-interferons in human pancreatic cell carcinoma lines and its implications for chemotherapy. Cancer Res 1996, 56:1083-1090.
117. Wang X., Li W., Zheng J., et al. Tumor suppressor gene alterations of spontaneously malignant transformed cells from human embryonic muscle in vitro. Oncol Rep 2010, 24:555-561.
118. Worsham M.J., Chen K.M., Tiwari N., et al. Fine-mapping loss of gene architecture at the CDKN2B (p15INK4b), CDKN2A (p14ARF, p16INK4a), and MTAP genes in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2006, 132:409-415.
119. Conway C., Beswick S., Elliott F., et al. Deletion at chromosome arm 9p in relation to BRAF/NRAS mutations and prognostic significance for primary melanoma. Genes Chromosomes Cancer 2010, 49:425-438.