Making the most of pathological specimens: Molecular diagnosis in formalin-fixed, paraffin embedded tissue

Current Drug Targets

Volumn 13, Issue 12, 2012, Pages 1475-1487

  Fairley, Jennifer A ^a   Gilmour, Katelyn ^a   Walsh, Kathy ^a  

^a ROYAL INFIRMARY OF EDINBURGH   (United Kingdom)

Author keywords

Biomarkers; BRAF; EGFR; FFPE diagnostics; FFPE tissue; HER2; KRAS; Molecular diagnostics; Molecular pathology; Personalised medicine; Targeted therapy

Indexed keywords

BIOLOGICAL MARKER; CETUXIMAB; CRIZOTINIB; ERLOTINIB; FORMALDEHYDE; GEFITINIB; IMATINIB; MICRORNA; PANITUMUMAB; PARAFFIN; TRASTUZUMAB; VEMURAFENIB;

ANAPLASTIC LYMPHOMA KINASE GENE; ARTICLE; B RAF KINASE GENE; BREAST CANCER; COLORECTAL CANCER; COMPARATIVE GENOMIC HYBRIDIZATION; EPIDERMAL GROWTH FACTOR RECEPTOR 2 GENE; EPIDERMAL GROWTH FACTOR RECEPTOR GENE; EPIGENETICS; FLUORESCENCE IN SITU HYBRIDIZATION; GASTROINTESTINAL STROMAL TUMOR; GENE; GENE EXPRESSION PROFILING; GENE MUTATION; GENE SEQUENCE; HUMAN; IMMUNOHISTOCHEMISTRY; LUNG ADENOCARCINOMA; LUNG NON SMALL CELL CANCER; MELANOMA; MOLECULAR DIAGNOSIS; NEOPLASM; ONCOGENE K RAS; PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN ANALYSIS; PROTEIN MICROARRAY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; STOMACH CANCER; TISSUE MICROARRAY;

ANIMALS; FIXATIVES; FORMALDEHYDE; GENETIC TECHNIQUES; GENOMICS; HUMANS; INDIVIDUALIZED MEDICINE; MOLECULAR TARGETED THERAPY; NEOPLASMS; PARAFFIN EMBEDDING; PATHOLOGY, MOLECULAR; PREDICTIVE VALUE OF TESTS; PROGNOSIS; PROTEOMICS; TISSUE FIXATION; TUMOR MARKERS, BIOLOGICAL;

EID: 84870197338     PISSN: 13894501     EISSN: 18735592     Source Type: Journal    
DOI: 10.2174/138945012803530125     Document Type: Article

References (132)

1. Wilkins B. The retention and storage of pathological records and specimens (4th edition, 2009). In: Guidance from The Royal College of Pathologists and the Institute of Biomedical Science. (2009).
2. Liszewski K. Applying aCGH to molecular diagnostics. Genetic Engineering and Biotechnology News 2008 28(10).
3. Hanahan D, Weinberg Robert A. Hallmarks of Cancer: The Next Generation. Cell 2011; 144(5): 646-674.
4. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344(11): 783-792.
5. Allegra CJ, Jessup JM, Somerfield MR, et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 2009; 27(12): 2091-2096.
6. Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26(10): 1626-1634.
7. Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from never smokers and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 2004; 101(36): 13306-13311.
8. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatinpaclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361(10): 947-957.
9. Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003; 21(23): 4342-4349.
10. Coussens L, Yang-Feng TL, Liao YC, et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 1985; 230(4730): 1132-1139.
11. Schechter AL, Hung MC, Vaidyanathan L, et al. The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 1985; 229(4717): 976-978.
12. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER- 2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244(4905): 707-712.
13. Neal DE, Marsh C, Bennett MK, et al. Epidermal-growth-factor receptors in human bladder cancer: comparison of invasive and superficial tumours. Lancet 1985; 1(8425): 366-368.
14. Kern JA, Schwartz DA, Nordberg JE, et al. P185neu expression in human lung adenocarcinomas predicts shortened survival. Cancer Res 1990; 50(16): 5184-5187.
15. Saffari B, Jones LA, el-Naggar A, Felix JC, George J, Press MF. Amplification and overexpression of HER-2/neu (c-erbB2) in endometrial cancers: correlation with overall survival. Cancer Res 1995; 55(23): 5693-5698.
16. Falck VG, Gullick WJ. C-erbB-2 oncogene product staining in gastric adenocarcinoma. An immunohistochemical study. J Pathol 1989; 159(2): 107-111.
17. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235(4785): 177-182.
18. Carter P, Presta L, Gorman CM, et al. Humanization of an antip185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 1992; 89(10): 4285-4289.
19. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353(16): 1673-1684.
20. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353(16): 1659-1672.
21. Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 2002; 20(3): 719-726.
22. Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol 2008; 19(9): 1523-1529.
23. Barbacid M. Ras oncogenes: their role in neoplasia. Eur J Clin Invest 1990; 20(3): 225-235.
24. Jonker DJ, O'Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007; 357(20): 2040-2048.
25. Pirker R, Pereira JR, Szczesna A, et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 2009; 373(9674): 1525-15231.
26. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008; 359(11): 1116-1127.
27. Ratner E, Lu L, Boeke M, et al. A KRAS-variant in ovarian cancer acts as a genetic marker of cancer risk. Cancer Res 2010; 70(16): 6509-6515.
28. Hutchins G, Southward K, Handley K, et al. Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer. J Clin Oncol 2011; 29(10): 1261-1270.
29. Heinemann V, Stintzing S, Kirchner T, Boeck S, Jung A. Clinical relevance of EGFR- and KRAS-status in colorectal cancer patients treated with monoclonal antibodies directed against the EGFR. Cancer Treat Rev 2009; 35(3): 262-271.
30. Adams RA, Meade AM, Madi A, et al. Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or without cetuximab in the MRC COIN trial experience. Br J Cancer 2009; 100(2): 251-258.
31. Smith G, Bounds R, Wolf H, Steele RJ, Carey FA, Wolf CR. Activating K-Ras mutations outwith 'hotspot' codons in sporadic colorectal tumours - implications for personalised cancer medicine. Br J Cancer 2010; 102(4): 693-703.
32. Modest DP, Jung A, Moosmann N, et al. The influence of KRAS and BRAF mutations on the efficacy of cetuximab-based first-line therapy of metastatic colorectal cancer: An analysis of the AIO KRK-0104-trial. Int J Cancer 2011; 131(4): 980-986.
33. Modest DP, Stintzing S, Laubender RP, et al. Clinical characterization of patients with metastatic colorectal cancer depending on the KRAS status. Anticancer Drugs 2011; 22(9): 913-918.
34. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999; 17(7): 2105-2116.
35. Puzanov I, Burnett P, Flaherty KT. Biological challenges of BRAF inhibitor therapy. Mol Oncol 2011; 5(2): 116-123.
36. Hoeflich KP, Herter S, Tien J, et al. Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression. Cancer Res 2009; 69(7): 3042-3051.
37. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364(26): 2507-2516.
38. Laurent-Puig P, Cayre A, Manceau G, et al. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol 2009; 27(35): 5924-5930.
39. Rizzo S, Bronte G, Fanale D, et al. Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy? Cancer Treat Rev 2010; 36 Suppl 3; S56-S561.
40. Lin JS, Webber EM, Senger CA, Holmes RS, Whitlock EP. Systematic review of pharmacogenetic testing for predicting clinical benefit to anti-EGFR therapy in metastatic colorectal cancer. Am J Cancer Res 2011; 1(5): 650-662.
41. de la Chapelle A, Hampel H. Clinical relevance of microsatellite instability in colorectal cancer. J Clin Oncol 2010; 28(20): 3380-3387.
42. Kerr DJ, Midgley R. Defective mismatch repair in colon cancer: a prognostic or predictive biomarker? J Clin Oncol 2010; 28(20): 3210-3212.
43. Sargent DJ, Marsoni S, Monges G, et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 2010; 28(20): 3219-3226.
44. Ng K, Schrag D. Microsatellite instability and adjuvant fluorouracil chemotherapy: a mismatch? J Clin Oncol 2010; 28(20): 3207-3210.
45. Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007; 7(3): 169-181.
46. Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med 2005; 353(2): 172-187.
47. Rich JN, Rasheed BK, Yan H. EGFR mutations and sensitivity to gefitinib. N Engl J Med 2004; 351(12): 1260-1261; author reply 1260-1261.
48. Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007; 7(3): 169-181.
49. Keedy VL, Temin S, Somerfield MR, et al. American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) Mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J Clin Oncol 2011; 29(15): 2121-2127.
50. Sasaki T, Rodig SJ, Chirieac LR, Janne PA. The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer 2010; 46(10): 1773-1780.
51. Gerber DE, Minna JD. ALK inhibition for non-small cell lung cancer: from discovery to therapy in record time. Cancer Cell 2010;18(6): 548-551.
52. Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical Features and Outcome of Patients With Non-Small-Cell Lung Cancer Who Harbor EML4-ALK. J Clin Oncol 2009; 27(26): 4247-4253.
53. Popat S, Vieira de Araujo A, Min T, et al. Lung adenocarcinoma with concurrent exon 19 EGFR mutation and ALK rearrangement responding to erlotinib. J Thorac Oncol 2011; 6(11): 1962-1963.
54. Qureshi HS, Linden MD, Divine G, Raju UB. E-cadherin status in breast cancer correlates with histologic type but does not correlate with established prognostic parameters. Am J Clin Pathol 2006; 125(3): 377-385.
55. Wallace WA. The challenge of classifying poorly differentiated tumours in the lung. Histopathology 2009; 54(1): 28-42.
56. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008; 26(21): 3543-3551.
57. Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 1998; 11(2): 155-168.
58. Harvey JM, Clark GM, Osborne CK, Allred DC. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 1999; 17(5): 1474-1481.
59. Gown AM. Current issues in ER and HER2 testing by IHC in breast cancer. Mod Pathol 2008; 21 Suppl 2: S8-S15.
60. Albain KS, Barlow WE, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomized trial. Lancet Oncol 2010; 11(1): 55-65.
61. Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 2010; 134(7): e48-e72.
62. Gurcan MN, Boucheron L, Can A, Madabhushi A, Rajpoot N, Yener B. Histopathological Image Analysis: A Review. IEEE Rev Biomed Eng 2009; 2: 147-171.
63. Thompson SL, Compton DA. Chromosomes and cancer cells. Chromosome Res 2011; 19(3): 433-444.
64. Drets ME, Shaw MW. Specific banding patterns of human chromosomes. Proc Natl Acad Sci USA 1971 68(9): 2073-2077.
65. Beeghly A, Katsaros D, Chen H, et al. Glutathione S-transferase polymorphisms and ovarian cancer treatment and survival. Gynecol Oncol 2006; 100(2): 330-337.
66. Helman LJ, Meltzer P. Mechanisms of sarcoma development. Nat Rev Cancer 2003; 3(9): 685-694.
67. Bilous M, Morey A, Armes J, Cummings M, Francis G. Chromogenic in situ hybridisation testing for HER2 gene amplification in breast cancer produces highly reproducible results concordant with fluorescence in situ hybridisation and immunohistochemistry. Pathology 2006; 38(2): 120-124.
68. Dietel M, Ellis IO, Hofler H, et al. Comparison of automated silver enhanced in situ hybridisation (SISH) and fluorescence ISH (FISH) for the validation of HER2 gene status in breast carcinoma according to the guidelines of the American Society of Clinical Oncology and the College of American Pathologists. Virchows Arch 2007; 451(1): 19-25.
69. Barberis M, Pellegrini C, Cannone M, Arizzi C, Coggi G, Bosari S. Quantitative PCR and HER2 testing in breast cancer: a technical and cost-effectiveness analysis. Am J Clin Pathol 2008; 129(4): 563-570.
70. Gnanapragasam VJ. Unlocking the molecular archive: the emerging use of formalin-fixed paraffin-embedded tissue for biomarker research in urological cancer. BJU Int 2010; 105(2): 274-278.
71. Quach N, Goodman M, Shibata D. In vitro mutation artifacts after formalin fixation and error prone translesion synthesis during PCR. BMC Clinical Pathology 2004; 4(1): 1.
72. Wong C, DiCioccio RA, Allen HJ, Werness BA, Piver MS. Mutations in BRCA1 from Fixed, Paraffin-Embedded Tissue Can Be Artifacts of Preservation. Cancer Genet Cytogenet 1998; 107(1): 21-27.
73. Bowler FR, Diaz-Mochon JJ, Swift MD, Bradley M. DNA Analysis by Dynamic Chemistry. Angew Chem Int Ed Engl 2010; 49(10): 1809-1812.
74. Fadhil W, Ibrahem S, Seth R, Ilyas M. Quick-multiplex-consensus (QMC)-PCR followed by high-resolution melting: a simple and robust method for mutation detection in formalin-fixed paraffinembedded tissue. J Clin Pathol 2010; 63(2): 134-140.
75. Ronaghi M, Uhlen M, Nyren P. A sequencing method based on real-time pyrophosphate. Science 1998; 281(5375): 363-365.
76. Ogino S, Kawasaki T, Brahmandam M, et al. Sensitive sequencing method for KRAS mutation detection by Pyrosequencing. J Mol Diagn 2005; 7(3): 413-421.
77. Krypuy M, Newnham GM, Thomas DM, Conron M, Dobrovic A. High resolution melting analysis for the rapid and sensitive detection of mutations in clinical samples: KRAS codon 12 and 13 mutations in non-small cell lung cancer. BMC Cancer 2006; 6: 295.
78. Li J, Wang L, Mamon H, Kulke MH, Berbeco R, Makrigiorgos GM. Replacing PCR with COLD-PCR enriches variant DNA sequences and redefines the sensitivity of genetic testing. Nat Med 2008; 14(5): 579-584.
79. Milbury CA, Li J, Makrigiorgos GM. Ice-COLD-PCR enables rapid amplification and robust enrichment for low-abundance unknown DNA mutations. Nucleic Acids Res 2011; 39(1): e2.
80. Thelwell N, Millington S, Solinas A, Booth J, Brown T. Mode of action and application of Scorpion primers to mutation detection. Nucleic Acids Res 2000; 28(19): 3752-3761.
81. Nagai Y, Miyazawa H, Huqun, et al. Genetic heterogeneity of the epidermal growth factor receptor in non-small cell lung cancer cell lines revealed by a rapid and sensitive detection system, the peptide nucleic acid-locked nucleic acid PCR clamp. Cancer Res 2005; 65(16): 7276-7282.
82. Thomas RK, Baker AC, Debiasi RM, et al. High-throughput oncogene mutation profiling in human cancer. Nat Genet 2007; 39(3): 347-351.
83. Fumagalli D, Gavin PG, Taniyama Y, et al. A rapid, sensitive, reproducible and cost-effective method for mutation profiling of colon cancer and metastatic lymph nodes. BMC Cancer 2010; 10: 101.
84. Kennedy GC, Matsuzaki H, Dong S, et al. Large-scale genotyping of complex DNA. Nat Biotechnol 2003; 21(10): 1233-1237.
85. de Jong D, Verbeke S, Meijer D, Hogendoorn PC, Bovee JV, Szuhai K. Opening the archives for state of the art tumour genetic research: sample processing for array-CGH using decalcified, formalin-fixed, paraffin-embedded tissue-derived DNA samples. BMC Res Notes 2011; 4: 1.
86. Little SE, Vuononvirta R, Reis-Filho JS, et al. Array CGH using whole genome amplification of fresh-frozen and formalin-fixed, paraffin-embedded tumor DNA. Genomics 2006; 87(2): 298-306.
87. McSherry EA, Mc Goldrick A, et al. Formalin-fixed paraffinembedded clinical tissues show spurious copy number changes in array-CGH profiles. Clin Genet 2007; 72(5): 441-447.
88. Gunn S, Yeh IT, Lytvak I, et al. Clinical array-based karyotyping of breast cancer with equivocal HER2 status resolves gene copy number and reveals chromosome 17 complexity. BMC Cancer 2010; 10: 396.
89. Greenman C, Stephens P, Smith R, et al. Patterns of somatic mutation in human cancer genomes. Nature 2007; 446(7132): 153-158.
90. Feinberg AP, Tycko B. The history of cancer epigenetics. Nat Rev Cancer 2004; 4(2): 143-153.
91. Mikeska T, Bock C, El-Maarri O, et al. Optimization of quantitative MGMT promoter methylation analysis using pyrosequencing and combined bisulfite restriction analysis. J Mol Diagn 2007; 9(3): 368-381.
92. Cokus SJ, Feng S, Zhang X, et al. Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature 2008; 452(7184): 215-219.
93. Wheeler DA, Srinivasan M, Egholm M, et al. The complete genome of an individual by massively parallel DNA sequencing. Nature 2008; 452(7189): 872-876.
94. Durbin RM, Abecasis GR, Altshuler DL, et al. A map of human genome variation from population-scale sequencing. Nature 2010; 467(7319): 1061-1073.
95. Lupski JR, Reid JG, Gonzaga-Jauregui C, et al. Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. N Engl J Med 2010; 362(13): 1181-1191.
96. Metzker ML. Sequencing technologies - the next generation. Nat Rev Genet 2010; 11(1): 31-46.
97. Voelkerding KV, Dames SA, Durtschi JD. Next-generation sequencing: from basic research to diagnostics. Clin Chem 2009; 55(4): 641-658.
98. Natrajan R, Reis-Filho JS. Next-generation sequencing applied to molecular diagnostics. Expert Rev Mol Diagn 2011; 11(4): 425-444.
99. Voelkerding KV, Dames S, Durtschi JD: Next generation sequencing for clinical diagnostics-principles and application to targeted resequencing for hyper trophic cardiomyopathy: a paper from the 2009 William Beaumont Hospital Symposium on Molecular Pathology. The Journal of molecular diagnostics: JMD 2010; 12(5): 539-551.
100. Varghese JS, Easton DF. Genome-wide association studies in common cancers--what have we learnt? Curr Opin Genet Dev 2010; 20(3): 201-209.
101. Stadler ZK, Vijai J, Thom P, et al. Genome-wide association studies of cancer predisposition. Hematol Oncol Clin North Am 2010; 24(5): 973-996.
102. Stadler ZK, Gallagher DJ, Thom P, Offit K. Genome-wide association studies of cancer: principles and potential utility. Oncology 2010; 24(7): 629-637.
103. Newport MJ, Finan C. Genome-wide association studies and susceptibility to infectious diseases. Brief Funct Genomics 2011; 10(2): 98-107.
104. Haack TB, Danhauser K, Haberberger B, et al. Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency. Nat Genet 2010; 42(12): 1131-134.
105. Shearer AE, DeLuca AP, Hildebrand MS, et al. Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing. Proc Natl Acad Sci USA 2010; 107(49): 21104-21109.
106. Timmermann B, Kerick M, Roehr C, et al. Somatic mutation profiles of MSI and MSS colorectal cancer identified by whole exome next generation sequencing and bioinformatics analysis. PloS one 2010; 5(12): e15661.
107. Lin J, Gan CM, Zhang X, et al. A multidimensional analysis of genes mutated in breast and colorectal cancers. Genome Res 2007; 17(9): 1304-1318.
108. Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008; 321(5897): 1801-1806.
109. Pfeifer GP, Hainaut P. Next-generation sequencing: emerging lessons on the origins of human cancer. Curr Opin Oncol 2011; 23(1): 62-68.
110. Pleasance ED, Stephens PJ, O'Meara S, et al. A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 2010; 463(7278): 184-190.
111. Raca G, Jackson C, Warman B, Bair T, Schimmenti LA. Next generation sequencing in research and diagnostics of ocular birth defects. Mol Genet Metab 2010; 100(2): 184-192.
112. Morgan JE, Carr IM, Sheridan E, et al. Genetic diagnosis of familial breast cancer using clonal sequencing. Hum Mutat 2010; 31(4): 484-491.
113. Schweiger MR, Kerick M, Timmermann B, et al. Genome-wide massively parallel sequencing of formaldehyde fixed-paraffin embedded (FFPE) tumor tissues for copy-number- and mutationanalysis. PloS one 2009; 4(5): e5548.
114. Kerick M, Isau M, Timmermann B, et al. Targeted high throughput sequencing in clinical cancer Settings: formaldehyde fixed-paraffin embedded (FFPE) tumor tissues, input amount and tumor heterogeneity. BMC Med Genomics 2011; 4: 68.
115. Tewhey R, Warner JB, Nakano M, et al. Micro droplet-based PCR enrichment for large-scale targeted sequencing. Nat Biotechnol 2009; 27(11): 1025-1031.
116. Clark MJ, Chen R, Lam HY, et al. Performance comparison of exome DNA sequencing technologies. Nat Biotechnol 2011; 29(10): 908-914.
117. Hedges DJ, Guettouche T, Yang S, et al. Comparison of three targeted enrichment strategies on the SOLiD sequencing platform. PLoS One 2011; 6(4): e18595.
118. Asan NF, Xu Y, Jiang H, et al. Comprehensive comparison of three commercial human whole-exome capture platforms. Genome Biol 2011; 12(9): R95.
119. Stein LD. The case for cloud computing in genome informatics. Genome Biol 2010; 11(5): 207.
120. Anderson L, Seilhamer J. A comparison of selected mRNA and protein abundances in human liver. Electrophoresis 1997; 18(3-4): 533-537.
121. Hood BL, Conrads TP, Veenstra TD. Unravelling the proteome of formalin-fixed paraffin-embedded tissue. Brief Funct Genomic Proteomic 2006; 5(2): 169-175.
122. Malinowsky K, Wolff C, Ergin B, Berg D, Becker KF. Deciphering signaling pathways in clinical tissues for personalized medicine using protein microarrays. J Cell Physiol 2010; 225(2): 364-370.
123. Varadhachary GR, Spector Y, Abbruzzese JL, et al. Prospective gene signature study using microRNA to identify the tissue of origin in patients with carcinoma of unknown primary. Clin Cancer Res 2011; 17(12): 4063-4070.
124. Lebanony D, Benjamin H, Gilad S, et al. Diagnostic assay based on hsa-miR-205 expression distinguishes squamous from nonsquamous non-small-cell lung carcinoma. J Clin Oncol 2009; 27(12): 2030-2037.
125. Penland SK, Keku TO, Torrice C, et al. RNA expression analysis of formalin-fixed paraffin-embedded tumors. Lab Invest 2007; 87(4): 383-391.
126. Monzon FA, Medeiros F, Lyons-Weiler M, Henner WD. Identification of tissue of origin in carcinoma of unknown primary with a microarray-based gene expression test. Diagn Pathol 2010; 5: 3.
127. Pentheroudakis G, Golfinopoulos V, Pavlidis N. Switching benchmarks in cancer of unknown primary: from autopsy to microarray. Eur J Cancer 2007; 43(14): 2026-2036.
128. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature 2000; 406(6797): 747-752.
129. Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinicalimplications. Proc Natl Acad Sci USA 2001; 98(19): 10869-10874.
130. Thomassen M, Tan Q, Eiriksdottir F, Bak M, Cold S, Kruse TA. Comparison of gene sets for expression profiling: prediction of metastasis from low-malignant breast cancer. Clin Cancer Res 2007; 13(18 Pt 1): 5355-5360.
131. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004; 351(27): 2817-2826.
132. Sparano JA. TAILORx: trial assigning individualized options for treatment (Rx). Clin Breast Cancer 2006; 7(4): 347-350