A 2015 update on predictive molecular pathology and its role in targeted cancer therapy: A review focussing on clinical relevance

Cancer Gene Therapy

Volumn 22, Issue 9, 2015, Pages 417-430

  Dietel, M ^a   Johrens K ^a   Laffert, M V ^a   Hummel, M ^a   Blaker H ^a   Pfitzner, B M ^a   Lehmann, A ^a   Denkert, C ^a   Darb Esfahani, S ^a   Lenze, D ^a   Heppner, F L ^a   Koch, A ^a   Sers, C ^a   Klauschen, F ^a   Anagnostopoulos, I ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

B RAF KINASE; BRCA1 PROTEIN; BRCA2 PROTEIN; DABRAFENIB; EPIDERMAL GROWTH FACTOR RECEPTOR; ISOCITRATE DEHYDROGENASE 1; ISOCITRATE DEHYDROGENASE 2; K RAS PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; TRAMETINIB; ANTINEOPLASTIC AGENT; DNA; TUMOR PROTEIN;

AMPLICON; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CANCER OF UNKNOWN PRIMARY SITE; CELL HETEROGENEITY; CENTRAL NERVOUS SYSTEM TUMOR; CHROMOSOME 19Q; CHROMOSOME 1P; CHROMOSOME ABERRATION; CHROMOSOME LOSS; COLORECTAL CANCER; COPY NUMBER VARIATION; DNA EXTRACTION; EXOME; GASTROINTESTINAL STROMAL TUMOR; GENE MUTATION; GENOME; GLIOMA; HAIRY CELL LEUKEMIA; HUMAN; LARGE CELL LYMPHOMA; MALIGNANT NEOPLASTIC DISEASE; MELANOMA; MOLECULAR DIAGNOSTICS; MOLECULAR PATHOLOGY; MOLECULARLY TARGETED THERAPY; MULTICENTER STUDY (TOPIC); NEXT GENERATION SEQUENCING; NON SMALL CELL LUNG CANCER; OVARY CANCER; PERSONALIZED MEDICINE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PREDICTIVE MOLECULAR PATHOLOGY; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEOMICS; QUALITY CONTROL; REVIEW; TUMOR CLASSIFICATION; WALDENSTROEM MACROGLOBULINEMIA; ANTAGONISTS AND INHIBITORS; DNA SEQUENCE; DRUG DESIGN; EXPERIMENTAL THERAPY; GENETICS; HIGH THROUGHPUT SEQUENCING; MOLECULAR DIAGNOSIS; MUTATION; NEOPLASMS; PATHOLOGY; PROCEDURES; TRENDS; TUMOR GENE;

ANTINEOPLASTIC AGENTS; CHROMOSOME ABERRATIONS; DNA, NEOPLASM; DRUG DESIGN; GENES, NEOPLASM; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MOLECULAR DIAGNOSTIC TECHNIQUES; MOLECULAR TARGETED THERAPY; MUTATION; NEOPLASM PROTEINS; NEOPLASMS; PRECISION MEDICINE; PROTEOMICS; SEQUENCE ANALYSIS, DNA; THERAPIES, INVESTIGATIONAL;

EID: 84942982171     PISSN: 09291903     EISSN: 14765500     Source Type: Journal    
DOI: 10.1038/cgt.2015.39     Document Type: Review

References (133)

1. Dietel M, Johrens K, Laffert M, Hummel M, Blaker H, Muller BM et al. Predictive molecular pathology and its role in targeted cancer therapy: a review focussing on clinical relevance. Cancer Gene Ther 2013; 20: 211-221.
2. Shaw AT, Kim DW, Nakagawa K, Seto T, Crino L, Ahn MJ et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013; 368: 2385-2394.
3. Willyard C. 'Basket studies' will hold intricate data for cancer drug approvals. Nat Med 2013; 19: 655.
4. Sleijfer S, Bogaerts J, Siu LL. Designing transformative clinical trials in the cancer genome era. J Clin Oncol 2013; 31: 1834-1841.
5. Duan N, Kravitz RL, Schmid CH. Single-patient (n-of-1) trials: a pragmatic clinical decision methodology for patient-centered comparative effectiveness research. J Clin Epidemiol 2013; 66: S21-S28.
6. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012; 489: 519-525.
7. Klauschen F, Andreeff M, Keilholz U, Dietel M, Stenzinger A. The combinatorial complexity of cancer precision medicine. Oncoscience 2014; 1: 504-509.
8. Kerick M, Isau M, Timmermann B, Sultmann H, Herwig R, Krobitsch S 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.
9. Collins FS. Hamburg MA. First FDA authorization for next-generation sequencer. N Engl J Med 2013; 369: 2369-2371.
10. Jamshidi F, Nielsen TO, Huntsman DG. Cancer genomics: why rare is valuable. J Mol Med 2015; 93: 369-381.
11. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 2014; 6: 224ra24.
12. Taguchi F, Solomon B, Gregorc V, Roder H, Gray R, Kasahara K et al. Mass spectrometry to classify non-small-cell lung cancer patients for clinical outcome after treatment with epidermal growth factor receptor tyrosine kinase inhibitors: a multi cohort cross-institutional study. J Natl Cancer Institute 2007; 99: 838-846.
13. Kuiper JL, Lind JS, Groen HJ, Roder J, Grigorieva J, Roder H et al. VeriStrat((R)) has prognostic value in advanced stage NSCLC patients treated with erlotinib and sorafenib. Br J Cancer 2012; 107: 1820-1825.
14. van Krieken JH, Normanno N, Blackhall F, Boone E, Botti G, Carneiro F et al. Guideline on the requirements of external quality assessment programs in molecular pathology. Virchows Arch 2013; 462: 27-37.
15. von Laffert M, Warth A, Penzel R, Schirmacher P, Kerr KM, Elmberger G et al. Multicenter immunohistochemical ALK-testing of non-small-cell lung cancer shows high concordance after harmonization of techniques and interpretation criteria. J Thorac Oncol 2014; 9: 1685-1692.
16. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA et al. Molecular portraits of human breast tumours. Nature 2000; 406: 747-752.
17. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 2013; 24: 2206-2223.
18. Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004; 351: 2817-2826.
19. Filipits M, Rudas M, Jakesz R, Dubsky P, Fitzal F, Singer CF et al. A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res 2011; 17: 6012-6020.
20. Gnant M, Filipits M, Greil R, Stoeger H, Rudas M, Bago-Horvath Z et al. Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. Ann Oncol 2014; 25: 339-345.
21. Dubsky P, Brase JC, Jakesz R, Rudas M, Singer CF, Greil R et al. The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2- breast cancer patients. Br J Cancer 2013; 109: 2959-2964.
22. Filipits M, Nielsen TO, Rudas M, Greil R, Stoger H, Jakesz R et al. The PAM50 riskof- recurrence score predicts risk for late distant recurrence after endocrine therapy in postmenopausal women with endocrine-responsive early breast cancer. Clin Cancer Res 2014; 20: 1298-1305.
23. Loibl S, von Minckwitz G, Schneeweiss A, Paepke S, Lehmann A, Rezai M et al. PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer. J Clin Oncol 2014; 32: 3212-3220.
24. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 2011; 474: 609-615.
25. Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer 2012; 12: 68-78.
26. Alsop K, Fereday S, Meldrum C, deFazio A, Emmanuel C, George J et al. BRCA mutation frequency and patterns of treatment response in BRCA mutationpositive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol 2012; 30: 2654-2663.
27. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012; 366: 1382-1392.
28. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol 2014; 15: 852-861.
29. Rigakos G, Razis E. BRCAness: finding the Achilles heel in ovarian cancer. Oncologist 2012; 17: 956-962.
30. Dann RB, DeLoia JA, Timms KM, Zorn KK, Potter J, Flake DD 2nd et al. BRCA1/2 mutations and expression: response to platinum chemotherapy in patients with advanced stage epithelial ovarian cancer. Gynecol Oncol 2012; 125: 677-682.
31. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ et al. Wildtype KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26: 1626-1634.
32. Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008; 359: 1757-1765.
33. De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol 2010; 11: 753-762.
34. Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M et al. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wildtype metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer 2012; 48: 1466-1475.
35. Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science 1993; 260: 816-819.
36. Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 1993; 363: 558-561.
37. Kim H, Jen J, Vogelstein B, Hamilton SR. Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol 1994; 145: 148-156.
38. Sargent DJ, Marsoni S, Monges G, Thibodeau SN, Labianca R, Hamilton SR 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: 3219-3226.
39. Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Institute 2004; 96: 261-268.
40. Kloor M, Voigt AY, Schackert HK, Schirmacher P, von Knebel Doeberitz M, Blaker H. Analysis of EPCAM protein expression in diagnostics of Lynch syndrome. J Clin Oncol 2011; 29: 223-227.
41. McCoach CE, Doebele RC. The minority report: targeting the rare oncogenes in NSCLC. Curr Treat Options Oncol 2014; 15: 644-657.
42. Thunnissen E, Bubendorf L, Dietel M, Elmberger G, Kerr K, Lopez-Rios F et al. EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations. Virchows Arch 2012; 461: 245-257.
43. Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Arch Pathol Lab Med 2013; 137: 828-860.
44. Reck M, Popat S, Reinmuth N, De Ruysscher D, Kerr KM, Peters S. Metastatic nonsmall- cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014; 25: iii27-iii39.
45. Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol 2011; 12: 1004-1012.
46. Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010; 363: 1693-1703.
47. Blackhall FH, Peters S, Bubendorf L, Dafni U, Kerr KM, Hager H et al. Prevalence and clinical outcomes for patients with ALK-positive resected stage I to III adenocarcinoma: results from the European Thoracic Oncology Platform Lungscape Project. J Clin Oncol 2014; 32: 2780-2787.
48. Sampsonas F, Ryan D, McPhillips D, Breen DP. Molecular testing and personalized treatment of lung cancer. Curr Mol Pharmacol 2014; 7: 22-32.
49. Stinchcombe TE. Novel agents in development for advanced non-small cell lung cancer. Ther Adv Med Oncol 2014; 6: 240-253.
50. Warth A, Stenzinger A, Weichert W. Novel morphological and molecular aspects of lung cancer. Der Pathologe 2013; 34: 419-428.
51. Powell CABE, Bubendorf L, Dacic S, Dziadziusko R, Geisinger K et al. Molecular testing for treatment selection in lung cancer. In: Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG (eds), WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th edn. 2015; Lyon, pp 22-25.
52. Yasuda H, Park E, Yun CH, Sng NJ, Lucena-Araujo AR, Yeo WL et al. Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med 2013; 5: 216ra177.
53. Arcila ME, Nafa K, Chaft JE, Rekhtman N, Lau C, Reva BA et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther 2013; 12: 220-229.
54. Tibaldi C. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small-cell lung cancer. Pharmacogenomics 2014; 15: 133-135.
55. Doebele RC, Pilling AB, Aisner DL, Kutateladze TG, Le AT, Weickhardt AJ et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res 2012; 18: 1472-1482.
56. Taniguchi K, Okami J, Kodama K, Higashiyama M, Kato K. Intratumor heterogeneity of epidermal growth factor receptor mutations in lung cancer and its correlation to the response to gefitinib. Cancer Sci 2008; 99: 929-935.
57. Ilie M, Hofman V, Long E, Bordone O, Selva E, Washetine K et al. Current challenges for detection of circulating tumor cells and cell-free circulating nucleic acids, and their characterization in non-small cell lung carcinoma patients. What is the best blood substrate for personalized medicine? Ann Transl Med 2014; 2: 107.
58. Bos M, Gardizi M, Schildhaus HU, Heukamp LC, Geist T, Kaminsky B et al. Complete metabolic response in a patient with repeatedly relapsed non-small cell lung cancer harboring ROS1 gene rearrangement after treatment with crizotinib. Lung Cancer 2013; 81: 142-143.
59. Ou SH, Kwak EL, Siwak-Tapp C, Dy J, Bergethon K, Clark JW et al. Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification. J Thorac Oncol 2011; 6: 942-946.
60. Jurmeister P, Lenze D, Berg E, Mende S, Schaper F, Kellner U et al. Parallel screening for ALK, MET and ROS1 alterations in non-small cell lung cancer with implications for daily routine testing. Lung Cancer 2015; 87: 122-129.
61. Yoshida A, Tsuta K, Wakai S, Arai Y, Asamura H, Shibata T et al. Immunohistochemical detection of ROS1 is useful for identifying ROS1 rearrangements in lung cancers. Mod Pathol 2014; 27: 711-720.
62. Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA 2007; 104: 20932-20937.
63. Spigel DR, Ervin TJ, Ramlau RA, Daniel DB, Goldschmidt JH Jr., Blumenschein GR Jr. et al. Randomized phase II trial of Onartuzumab in combination with erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol 2013; 31: 4105-4114.
64. Frampton GM, Ali SM, Rosenzweig M, Chmielecki J, Lu X, Bauer TM et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov 2015; 5: 850-859.
65. Hirsch FR, Bunn PA Jr.. Herbst RS. 'Companion diagnostics': has their time come and gone? Clin Cancer Res 2014; 20: 4422-4424.
66. Vijayvergia N, Mehra R. Clinical challenges in targeting anaplastic lymphoma kinase in advanced non-small cell lung cancer. Cancer Chem Pharmacol 2014; 74: 437-446.
67. Erickson C, Driscoll MS. Melanoma epidemic: facts and controversies. Clin Dermatol 2010; 28: 281-286.
68. McArthur GA, Chapman PB, Robert C, Larkin J, Haanen JB, Dummer R et al. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, openlabel study. Lancet Oncol 2014; 15: 323-332.
69. Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012; 380: 358-365.
70. Tronnier M, Mitteldorf C. Treating advanced melanoma: current insights and opportunities. Cancer Management Res 2014; 6: 349-356.
71. Livingstone E, Zimmer L, Vaubel J, Schadendorf D. BRAF, MEK and KIT inhibitors for melanoma: adverse events and their management. Chinese Clin Oncol 2014; 3: 29.
72. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 2010; 464: 427-430.
73. Dinges HC, Capper D, Ritz O, Bruderlein S, Marienfeld R, von Deimling A et al. Validation of a manual protocol for BRAF V600E mutation-specific immunohistochemistry. Appl Immunohistochem Mol Morphol 2015; 23: 382-388.
74. Jakob JA, Bassett RL Jr., Ng CS, Curry JL, Joseph RW, Alvarado GC et al. NRAS mutation status is an independent prognostic factor in metastatic melanoma. Cancer 2012; 118: 4014-4023.
75. Torres-Cabala CA, Wang WL, Trent J, Yang D, Chen S, Galbincea J et al. Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acral-lentiginous/mucosal type. Mod Pathol 2009; 22: 1446-1456.
76. Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med 2012; 367: 1694-1703.
77. Morris EJ, Jha S, Restaino CR, Dayananth P, Zhu H, Cooper A et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov 2013; 3: 742-750.
78. Hu-Lieskovan S, Robert L, Homet Moreno B, Ribas A. Combining targeted therapy with immunotherapy in BRAF-mutant melanoma: promise and challenges. J Clin Oncol 2014; 32: 2248-2254.
79. Pentheroudakis G, Golfinopoulos V, Pavlidis N. Switching benchmarks in cancer of unknown primary: from autopsy to microarray. Eur J Cancer 2007; 43: 2026-2036.
80. Pavlidis N, Fizazi K. Carcinoma of unknown primary (CUP). Crit Rev Oncol 2009; 69: 271-278.
81. Greco FA, Pavlidis N. Treatment for patients with unknown primary carcinoma and unfavorable prognostic factors. Semin Oncol 2009; 36: 65-74.
82. Ma XJ, Patel R, Wang X, Salunga R, Murage J, Desai R et al. Molecular classification of human cancers using a 92-gene real-time quantitative polymerase chain reaction assay. Arch Pathol Lab Med 2006; 130: 465-473.
83. Pillai R, Deeter R, Rigl CT, Nystrom JS, Miller MH, Buturovic L et al. Validation and reproducibility of a microarray-based gene expression test for tumor identification in formalin-fixed, paraffin-embedded specimens. J Mol Diagn 2011; 13: 48-56.
84. Meiri E, Mueller WC, Rosenwald S, Zepeniuk M, Klinke E, Edmonston TB et al. A second-generation microRNA-based assay for diagnosing tumor tissue origin. Oncologist 2012; 17: 801-812.
85. Greco FA, Lennington WJ, Spigel DR, Hainsworth JD. Molecular profiling diagnosis in unknown primary cancer: accuracy and ability to complement standard pathology. J Natl Cancer Institute 2013; 105: 782-790.
86. Weiss LM, Chu P, Schroeder BE, Singh V, Zhang Y, Erlander MG et al. Blinded comparator study of immunohistochemical analysis versus a 92-gene cancer classifier in the diagnosis of the primary site in metastatic tumors. J Mol Diagn 2013; 15: 263-269.
87. Handorf CR, Kulkarni A, Grenert JP, Weiss LM, Rogers WM, Kim OS et al. A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors. Am J Surg Pathol 2013; 37: 1067-1075.
88. Tsimberidou AM, Iskander NG, Hong DS, Wheler JJ, Falchook GS, Fu S et al. Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative. Clin Cancer Res 2012; 18: 6373-6383.
89. Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-Bcell lymphoma. N Engl J Med 2002; 346: 1937-1947.
90. Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H et al. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 2008; 359: 2313-2323.
91. Meyer PN, Fu K, Greiner TC, Smith LM, Delabie J, Gascoyne RD et al. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab. J Clin Oncol 2011; 29: 200-207.
92. Savage KJ, Johnson NA, Ben-Neriah S, Connors JM, Sehn LH, Farinha P et al. MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy. Blood 2009; 114: 3533-3537.
93. Barrans S, Crouch S, Smith A, Turner K, Owen R, Patmore R et al. Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma treated in the era of rituximab. J Clin Oncol 2010; 28: 3360-3365.
94. Friedberg JW. Double-hit diffuse large B-cell lymphoma. J Clin Oncol 2012; 30: 3439-3443.
95. Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol 2012; 30: 3452-3459.
96. Green TM, Young KH, Visco C, Xu-Monette ZY, Orazi A, Go RS et al. Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol 2012; 30: 3460-3467.
97. Hu S, Xu-Monette ZY, Tzankov A, Green T, Wu L, Balasubramanyam A et al. MYC/ BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program. Blood 2013; 121: 4021-4031 quiz 4250.
98. Goodman GR, Bethel KJ, Saven A. Hairy cell leukemia: an update. Curr Opin Hematol 2003; 10: 258-266.
99. Matutes E, Wotherspoon A, Catovsky D. The variant form of hairy-cell leukaemia. Best Pract Res Clin Haematol 2003; 16: 41-56.
100. Arons E, Kreitman RJ. Molecular variant of hairy cell leukemia with poor prognosis. Leuk Lymphoma 2011; 52: 99-102.
101. Tiacci E, Schiavoni G, Forconi F, Santi A, Trentin L, Ambrosetti A et al. Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAFV600E mutation. Blood 2012; 119: 192-195.
102. Xi L, Arons E, Navarro W, Calvo KR, Stetler-Stevenson M, Raffeld M et al. Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation. Blood 2012; 119: 3330-3332.
103. Jain P, Polliack A, Ravandi F. Novel therapeutic options for relapsed hairy cell leukemia. Leuk Lymphoma 2015; 4: 1-9.
104. Treon SP, Cao Y, Xu L, Yang G, Liu X, Hunter ZR. Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemia. Blood 2014; 123: 2791-2796.
105. Corless CL, Heinrich MC. Molecular pathobiology of gastrointestinal stromal sarcomas. Annu Rev Pathol 2008; 3: 557-586.
106. Miettinen M, Lasota J. Gastrointestinal stromal tumors. Gastroenterol Clin North Am 2013; 42: 399-415.
107. Agaram NP, Wong GC, Guo T, Maki RG, Singer S, Dematteo RP et al. Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors. Genes Chromosomes Cancer 2008; 47: 853-859.
108. Taylor BS, Barretina J, Maki RG, Antonescu CR, Singer S, Ladanyi M. Advances in sarcoma genomics and new therapeutic targets. Nature Rev Cancer 2011; 11: 541-557.
109. Maertens O, Prenen H, Debiec-Rychter M, Wozniak A, Sciot R, Pauwels P et al. Molecular pathogenesis of multiple gastrointestinal stromal tumors in NF1 patients. Hum Mol Genet 2006; 15: 1015-1023.
110. Blay JY, Rutkowski P. Adherence to imatinib therapy in patients with gastrointestinal stromal tumors. Cancer Treat Rev 2014; 40: 242-247.
111. Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 373: 1097-1104.
112. DeMatteo RP, Ballman KV, Antonescu CR, Corless C, Kolesnikova V, von Mehren M et al. Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumor: ACOSOG Z9000 (Alliance) intergroup phase 2 trial. Ann Surg 2013; 258: 422-429.
113. Corless CL, Schroeder A, Griffith D, Town A, McGreevey L, Harrell P et al. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 2005; 23: 5357-5364.
114. Lee JH, Kim Y, Choi JW, Kim YS. Correlation of imatinib resistance with the mutational status of KIT and PDGFRA genes in gastrointestinal stromal tumors: a meta-analysis. J Gastrointest Liv Dis 2013; 22: 413-418.
115. Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT et al. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 2006; 42: 1093-1103.
116. Heng DY, Kollmannsberger C. Sunitinib. Recent Results Cancer Res 2010; 184: 71-82.
117. Patel S. Managing progressive disease in patients with GIST: factors to consider besides acquired secondary tyrosine kinase inhibitor resistance. Cancer Treat Rev 2012; 38: 467-472.
118. Shern JF, Chen L, Chmielecki J, Wei JS, Patidar R, Rosenberg M et al. Comprehensive genomic analysis of rhabdomyosarcoma reveals a landscape of alterations affecting a common genetic axis in fusion-positive and fusionnegative tumors. Cancer Discov 2014; 4: 216-231.
119. Wagner LM, Fouladi M, Ahmed A, Krailo MD, Weigel B, DuBois SG et al. Phase II study of cixutumumab in combination with temsirolimus in pediatric patients and young adults with recurrent or refractory sarcoma: a report from the Children's Oncology Group. Pediatr Blood Cancer 2015; 62: 440-444.
120. Weiss A, Gill J, Goldberg J, Lagmay J, Spraker-Perlman H, Venkatramani R et al. Advances in therapy for pediatric sarcomas. Current Oncol Rep 2014; 16: 395.
121. Crompton BD, Stewart C, Taylor-Weiner A, Alexe G, Kurek KC, Calicchio ML et al. The genomic landscape of pediatric Ewing sarcoma. Cancer Discov 2014; 4: 1326-1341.
122. Tirode F, Surdez D, Ma X, Parker M, Le Deley MC, Bahrami A et al. Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations. Cancer Discov 2014; 4: 1342-1353.
123. Sand LG, Szuhai K, Hogendoorn PC. Sequencing overview of Ewing Sarcoma: a journey across genomic, epigenomic and transcriptomic landscapes. Int J Mol Sci 2015; 16: 16176-16215.
124. Agelopoulos K, Richter GH, Schmidt E, Dirksen U, von Heyking K, Moser B et al. Deep sequencing in conjunction with expression and functional analyses reveals activation of FGFR1 in Ewing sarcoma. Clin Cancer Res.
125. July 2015. pii: clincanres.2744.2014 (e-pub ahead of print).
126. Chen X, Bahrami A, Pappo A, Easton J, Dalton J, Hedlund E et al. Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma. Cell Rep 2014; 7: 104-112.
127. Wang H, Yang Q, Fu Z, Zuo D, Hua Y, Cai Z. ErbB receptors as prognostic and therapeutic drug targets in bone and soft tissue sarcomas. Cancer Invest 2014; 32: 533-542.
128. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007; 114: 97-109.
129. Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J et al. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 2013; 31: 337-343.
130. van den Bent MJ, Brandes AA, Taphoorn MJ, Kros JM, Kouwenhoven MC, Delattre JY et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 2013; 31: 344-350.
131. Malmstrom A, Gronberg BH, Marosi C, Stupp R, Frappaz D, Schultz H et al. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 2012; 13: 916-926.
132. Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M et al. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol 2012; 13: 707-715.
133. Louis DN, Perry A, Burger P, Ellison DW, Reifenberger G, von Deimling A et al. International Society Of Neuropathology-Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol 2014; 24: 429-435.