Karyotypic Complexity of the NCI-60 Drug-Screening Panel

Cancer Research

Volumn 63, Issue 24, 2003, Pages 8634-8647

  Roschke, Anna V ^a   Tonon, Giovanni ^a   Gehlhaus, Kristen S ^a   McTyre, Nicolas ^a   Bussey, Kimberly J ^a   Lababidi, Samir ^a   Scudiero, Dominic A ^b   Weinstein, John N ^a   Kirsch, Ilan R ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b SAIC FREDERICK INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MOLECULAR MARKER; PROTEIN P53; RETINOBLASTOMA PROTEIN; TUMOR MARKER;

ARTICLE; CANCER CELL CULTURE; CARCINOGENESIS; CELL HETEROGENEITY; CELL LINE; CELL LINEAGE; CENTROMERE; CHROMOSOMAL INSTABILITY; CHROMOSOME ABERRATION; CHROMOSOME STRUCTURE; CHROMOSOME TRANSLOCATION; CONTROLLED STUDY; DATA BASE; DNA REPAIR; DRUG RESISTANCE; DRUG SCREENING; DRUG SENSITIVITY; EPITHELIUM CELL; GENE DOSAGE; GENE EXPRESSION; GENE TARGETING; GENETICS; GENOME; GENOME ANALYSIS; HEMATOPOIETIC SYSTEM TUMOR; HUMAN; HUMAN CELL; KARYOTYPE; KARYOTYPING; METAPHASE; NCI 60 DRUG SCREENING PANEL; NEOPLASM; PATHOLOGY; PLOIDY; PRIORITY JOURNAL; SPECTRAL KARYOTYPING; TUMOR CELL LINE; TUMOR GROWTH;

CELL LINE, TUMOR; CHROMOSOME ABERRATIONS; DNA REPAIR; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; NEOPLASMS; PLOIDIES; RETINOBLASTOMA PROTEIN; SPECTRAL KARYOTYPING; TRANSLOCATION, GENETIC; TUMOR SUPPRESSOR PROTEIN P53;

EID: 0347951257     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (76)

1. Shoemaker, R. H., Monks, A., Alley, M. C., Scudiero, D. A., Fine, D. L., McLemore, T. L., Abbott, B. J., Paull, K. D., Mayo, J. G., and Boyd, M. R. Development of human tumor cell line panels for use in disease-oriented drug screening. Prog. Clin. Biol. Res., 276: 265-286, 1988.
2. Monks, A., Scudiero, D., Skehan, P., Shoemaker, R., Paull, K., Vistica, D., Hose, C., Langley, J., Cronise, P., Vaigro-Wolff, A., et al. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J. Natl. Cancer Inst., 83: 757-766. 1991.
3. Monks, A., Scudiero, D. A., Johnson, G. S., Paull, K. D., and Sausville, E. A. The NCI anti-cancer drug screen: a smart screen to identify effectors of novel targets. Anticancer Drug Des., 12: 533-541, 1997.
4. Grever, M. R., Schepartz, S. A., and Chabner, B. A. The National Cancer Institute: cancer drug discovery and development program. Semin. Oncol., 19: 622-638, 1992.
5. Stinson, S. F., Alley, M. C., Kopp, W. C., Fiebig, H. H., Mullendore, L. A., Pittman, A. F., Kenney, S., Keller, J., and Boyd, M. R. Morphological and immunocytochemical characteristics of human tumor cell lines for use in a disease-oriented anticancer drug screen. Anticancer Res., 12: 1035-1053, 1992.
6. Bates, S. E., Fojo, A. T., Weinstein, J. N., Myers, T. G., Alvarez, M., Pauli, K. D., and Chabner, B. A. Molecular targets in the National Cancer Institute drug screen. J. Cancer Res. Clin. Oncol., 121: 495-500, 1995.
7. Weinstein, J. N., Kohn, K. W., Grever, M. R., Viswanadhan, V. N., Rubinstein, L. V., Monks, A. P., Scudiero, D. A., Welch, L., Koutsoukos, A. D., Chiausa, A. J., and et al. Neural computing in cancer drug development: predicting mechanism of action. Science (Wash. DC), 258: 447-451, 1992.
8. Weinstein, J. N., Myers, T. G., O'Connor, P. M., Friend, S. H., Fornace, A. J., Jr., Kohn, K. W., Fojo, T., Bates, S. E., Rubinstein, L. V., Anderson, N. L., Buolamwini, J. K., van Osdol, W. W., Monks, A. P., Scudiero, D. A., Sausville, E. A., Zaharevitz, D. W., Bunow, B., Viswanadhan, V. N., Johnson, G. S., Wittes, R. E., and Paull, K. D. An information-intensive approach to the molecular pharmacology of cancer. Science (Wash. DC), 275: 343-349, 1997.
9. O'Connor, P. M., Jackman, J., Bae, I., Myers, T. G., Fan, S., Mutoh, M., Scudiero, D. A., Monks, A., Sausville, E. A., Weinstein, J. N., Friend, S., Fornace, A. J., Jr., and Kohn, K. W., Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents. Cancer Res., 57: 4285-4300, 1997.
10. Ross, D. T., Scherf, U., Eisen, M. B., Perou, C. M., Rees, C., Spellman, P., Iyer, V., Jeffrey, S. S., Van de Rijn, M., Waltham, M., Pergamenschikov, A., Lee, J. C., Lashkari, D., Shalon, D., Myers, T. G., Weinstein, J. N., Botstein, D., and Brown, P. O. Systematic variation in gene expression patterns in human cancer cell lines. Nat. Genet., 24: 227-235, 2000.
11. Scherf, U., Ross, D. T., Waltham, M., Smith, L. H., Lee, J. K., Tanabe, L., Kohn, K. W., Reinhold, W. C., Myers, T. G., Andrews, D. T., Scudiero, D. A., Eisen, M. B., Sausville, E. A., Pommier, Y., Botstein, D., Brown, P. O., and Weinstein, J. N. A gene expression database for the molecular pharmacology of cancer. Nat. Genet., 24: 236-244, 2000.
12. Staunton, J. E., Slonim, D. K., Coller, H. A., Tamayo, P., Angelo, M. J., Park, J., Scherf, U., Lee, J. K., Reinhold, W. O., Weinstein, J. N., Mesirov, J. P., Lander, E. S., and Golub, T. R. Chemosensitivity prediction by transcriptional profiling. Proc Natl. Acad. Sci. USA, 98: 10787-10792, 2001.
13. Modi, W. S., Nash, W. G., Ferrari, A. C., and O'Brien, S. J. Cytogenetic methodologies for gene mapping and comparative analyses in mammalian cell culture systems. Gene Anal. Tech., 4: 75-85, 1987.
14. Schröck, E., du Manoir, S., Veldman, T., Schoell, B., Wienberg, J., Ferguson-Smith, M. A., Ning, Y., Ledbetter, D. H., Bar-Am, I., Soenksen, D., Garini, Y., and Ried, T. Multicolor spectral karyotyping of human chromosomes [see comments]. Science (Wash. DC), 273: 494-497, 1996.
15. Roschke, A. V., Stover, K., Tonon, G., Schaffer, A. A., and Kirsch, I. R. Stable karyotypes in epithelial cancer cell lines despite high rates of ongoing structural and numerical chromosomal instability. Neoplasia, 4: 19-31, 2002.
16. Mitelman, F. (Ed.) ISCN (1995): An International System for Human Cytogenetic Nomenclature. Basel: S. Karger, 1995.
17. Tonon. G., Roschke, A., Stover, K., Shou, Y., Kuehl, W. M., and Kirsch, I. R. Spectral karyotyping combined with locus-specific FISH simultaneously defines genes and chromosomes involved in chromosomal translocations. Genes Chromosomes Cancer, 27: 418-423, 2000.
18. Kirsch, I. R., Green, E. D., Yonescu, R., Strausberg, R., Carter, N., Bentley, D., Leversha, M. A., Dunham, I., Braden, V. V., Hilgenfeld, E., Schuler, G., Lash, A. E., Shen, G. L., Martelli, M., Kuehl, W. M., Klausner, R. D., and Ried, T. A systematic, high-resolution linkage of the cytogenetic and physical maps of the human genome. Nat. Genet., 24: 339-340, 2000.
19. Padilla-Nash, H. M., Heselmeyer-Haddad, K., Wangsa, D., Zhang, H., Ghadimi, B. M., Macville, M., Augustus, M., Schröck, E., Hilgenfeld, E., and Ried, T. Jumping translocations are common in solid tumor cell lines and result in recurrent fusions of whole chromosome arms. Genes Chromosomes Cancer, 30: 349-363, 2001.
20. Atkin, N. B., and Baker, M. C. Small metacentric marker chromosomes, particularly isochromosomes, in cancer. Hum Genet, 79: 96-102, 1988.
21. Mitelman, F., Johansson, B., and Mertens, F. (Eds.) Mitelman Database of Chromosome Aberrations in Cancer, http://cgap.nci.nih.gov/Chromosomes/Mitelman, 2003.
22. Taverna, P., Liu, L., Hanson, A. J., Monks, A., and Gerson, S. L. Characterization of MLH1 and MSH2 DNA mismatch repair proteins in cell lines of the NCI anticancer drug screen. Cancer Chemother. Pharmacol., 46: 507-516, 2000.
23. Ohzeki, S., Tachibana, A., Tatsumi, K., and Kato, T. Spectra of spontaneous mutations at the hprt locus in colorectal carcinoma cell lines defective in mismatch repair. Carcinogenesis (Lond.), 18: 1127-1133, 1997.
24. Aurich-Costa, J., Vannier, A., Gregoire, E., Nowak, F., and Cherif, D. IPM-FISH, a new M-FISH approach using IRS-PCR painting probes: application to the analysis of seven human prostate cell lines. Genes Chromosomes Cancer, 30: 143-160, 2001.
25. Davidson, J. M., Gorringe, K. L., Chin, S. F., Orsetti, B., Besret, C., Courtay-Cahen, C., Roberts, I., Theillet, C., Caldas, C., and Edwards, P. A. Molecular cytogenetic analysis of breast cancer cell lines. Br. J. Cancer, 83: 1309-1317, 2000.
26. Gribble, S. M., Roberts, I., Grace, C., Andrews, K. M., Green, A. R., and Nacheva, E. P. Cytogenetics of the chronic myeloid leukemia-derived cell line K562: karyotype clarification by multicolor fluorescence in situ hybridization, comparative genomic hybridization, and locus-specific fluorescence in situ hybridization. Cancer Genet. Cytogenet., 118: 1-8, 2000.
27. Kawai, K., Viars, C., Arden, K., Tarin, D., Urquidi, V., and Goodison, S. Comprehensive karyotyping of the HT-29 colon adenocarcinoma cell line. Genes Chromosomes Cancer, 34: 1-8, 2002.
28. Kytölä, S., Rummukainen, J., Nordgren, A., Karhu, R., Farnebo, F., Isola, J., and Larsson, C. Chromosomal alterations in 15 breast cancer cell lines by comparative genomic hybridization and spectral karyotyping. Genes Chromosomes Cancer, 28: 308-317, 2000.
29. Lu, Y. J., Morris, J. S., Edwards, P. A., and Shipley, J. Evaluation of 24-color multifluor-fluorescence in-situ hybridization (M-FISH) karyotyping by comparison with reverse chromosome painting of the human breast cancer cell line T-47D. Chromosome Res., 8: 127-132, 2000.
30. Luk, C., Tsao, M. S., Bayani, J., Shepherd, F., and Squire, J. A. Molecular cytogenetic analysis of non-small cell lung carcinoma by spectral karyotyping and comparative genomic hybridization. Cancer Genet. Cytogenet., 125: 87-99, 2001.
31. Masramon, L., Ribas, M., Cifuentes, P., Arribas, R., García, F., Egozcue, J., Peinado, M. A., and Miró, R. Cytogenetic characterization of two colon cell lines by using conventional G-banding, comparative genomic hybridization, and whole chromosome painting. Cancer Genet. Cytogenet., 121: 17-21, 2000.
32. Melcher, R., Koehler, S., Steinlein, C., Schmid, M., Mueller, C. R., Luehrs, H., Menzel, T., Scheppach, W., Moerk, H., Scheurlen, M., Koehrle, J., and Al-Taie, O. Spectral karyotype analysis of colon cancer cell lines of the tumor suppressor and mutator pathway. Cytogenet. Genome Res., 98: 22-28, 2002.
33. Pan, Y., Lui, W. O., Nupponen, N., Larsson, C., Isola, J., Visakorpi, T., Bergerheim, U. S., and Kytola, S. 5q11, 8p11, and 10q22 are recurrent chromosomal breakpoints in prostate cancer cell lines. Genes Chromosomes Cancer, 30: 187-195, 2001.
34. Popovici, C., Basset, C., Bertucci, F., Orsetti, B., Adélaide, J., Mozziconacci, M. J., Conte, N., Murati, A., Ginestier, C., Charafe-Jauffret, E., Ethier, S. P., Lafage-Pochitaloff, M., Theillet, C., Bimbaum, D., and Chaffanet, M. Reciprocal translocations in breast tumor cell lines: cloning of a t(3;20) that targets the FHIT gene. Genes Chromosomes Cancer, 35: 204-218, 2002.
35. Rao, P. H., Harris, C. P., Yan Lu, X., Li, X. N., Mok, S. C., and Lau, C. C. Multicolor spectral karyotyping of serous ovarian adenocarcinoma. Genes Chromosomes Cancer, 33: 123-132, 2002.
36. Strefford, J. C., Lillington, D. M., Young, B. D., and Oliver, R. T. The use of multicolor fluorescence technologies in the characterization of prostate carcinoma cell lines: a comparison of multiplex fluorescence in situ hybridization and spectral karyotyping data. Cancer Genet. Cytogenet., 124: 112-121, 2001.
37. Varella-Garcia, M., Boomer, T., and Miller, G. J. Karyotypic similarity identified by multiplex-FISH relates four prostate adenocarcinoma cell lines: PC-3, PPC-1, ALVA-31, and ALVA-41. Genes Chromosomes Cancer, 31: 303-315, 2001.
38. Mitelman, F., Johansson, B., and Mertens, F. Catalog of chromosome aberrations in cancer, Ed. 5, p. 2 v. (xxix, 4252). New York: Wiley-Liss, 1994.
39. Johansson, B., Mertens, F., and Mitelman, F. Primary vs. secondary neoplasia-associated chromosomal abnormalities-balanced rearrangements vs. genomic imbalances?. Genes Chromosomes Cancer, 16: 155-163, 1996.
40. Chen, T. R., Drabkowski, D., Hay, R. J., Macy, M., and Peterson, W., Jr. WiDr is a derivative of another colon adenocarcinoma cell line, HT-29. Cancer Genet. Cytogenet., 27: 125-134, 1987.
41. Macville, M., Schrock, E., Padilla-Nash, H., Keck, C., Ghadimi, B. M., Zimonjic, D., Popescu, N., and Ried, T. Comprehensive and definitive molecular cytogenetic characterization of HeLa cells by spectral karyotyping. Cancer Res., 59: 141-150, 1999.
42. Knutsen, T. V., Rao, K., Ried, T., Mickley, L., Schneider, E., Miyake, K., Ghadimi, M., Padilla-Nash, H., Pack, S., Greenberger, L., Cowan, K., Dean, M., Fojo, T., and Bates, S. Amplification of 4q21-q22 and the MXR gene in independently derived mitoxantrone-resistant cell lines. Genes Chromosomes Cancer, 27: 110-116, 2000.
43. Reinhold, W. C., Kouros-Mehr, H., Kohn, K. W., Maunakea, A. K., Lababidi, S., Roschke, A., Stover, K., Alexander, J., Pantazis, P., Miller, L., Liu, E., Kirsch, I. R., Urasaki, Y., Pommier, Y., and Weinstein, J. N. Apoptotic susceptibility of cancer cells selected for camptothecin resistance: gene expression profiling, functional analysis, and molecular interaction mapping. Cancer Res., 63: 1000-1011, 2003.
44. Fabarius, A., Hehlmann, R., and Duesberg, P. H. Instability of chromosome structure in cancer cells increases exponentially with degrees of aneuploidy. Cancer Genet. Cytogenet., 143: 59-72, 2003.
45. Rooney, P. H., Murray, G. I., Stevenson, D. A., Haites, N. E., Cassidy, J., and McLeod, H. L. Comparative genomic hybridization and chromosomal instability in solid tumours. Br. J. Cancer, 80: 862-873, 1999.
46. Mitelman, F., Johansson, B., Mandahl, N., and Mertens, F. Clinical significance of cytogenetic findings in solid tumors. Cancer Genet. Cytogenet., 95: 1-8, 1997.
47. Höglund, M., Gisselsson, D., Mandahl, N., Johansson, B., Mertens, F., Mitelman, F., and Sall, T. Multivariate analyses of genomic imbalances in solid tumors reveal distinct and converging pathways of karyotypic evolution. Genes Chromosomes Cancer, 31: 156-171, 2001.
48. Höglund, M., Gisselsson, D., Hansen, G. B., Säll, T., and Mitelman, F. Multivariate analysis of chromosomal imbalances in breast cancer delineates cytogenetic pathways and reveals complex relationships among imbalances. Cancer Res., 62: 2675-2680, 2002.
49. Bastian, B. C., LeBoit, P. E., Hamm, H., Brocker, E. B., and Pinkel, D. Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res., 58: 2170-2175, 1998.
50. Balázs, M., Adám, Z., Treszl, A., Bégány, A., Hunyadi, J., and Adány, R. Chromosomal imbalances in primary and metastatic melanomas revealed by comparative genomic hybridization. Cytometry, 46: 222-232, 2001.
51. Ried, T., Knutzen, R., Steinbeck, R., Blegen, H., Schröck, E., Heselmeyer, K., du Manoir, S., and Auer, G. Comparative genomic hybridization reveals a specific pattern of chromosomal gains and losses during the genesis of colorectal tumors. Genes Chromosomes Cancer, 15: 234-245, 1996.
52. Jenkins, R. B., Bartelt, D., Jr., Stalboerger, P., Persons, D., Dahl, R. J., Podratz, K., Keeney, G., and Hartmann, L. Cytogenetic studies of epithelial ovarian carcinoma. Cancer Genet. Cytogenet., 71: 76-86, 1993.
53. Blegen, H., Einhorn, N., Sjövall, K., Roschke, A., Ghadimi, B. M., McShane, L. M., Nilsson, B., Shah, K., Ried, T., and Auer, G. Prognostic significance of cell cycle proteins and genomic instability in borderline, early and advanced stage ovarian carcinomas. Int. J. Gynecol. Cancer, 10: 477-487, 2000.
54. Teixeira, M. R., Pandis, N., and Heim, S. Cytogenetic clues to breast carcinogenesis. Genes Chromosomes Cancer, 33: 1-16, 2002.
55. Taetle, R., Aickin, M., Yang, J. M., Panda, L., Emerson, J., Roe, D., Adair, L., Thompson, F., Liu, Y., Wisner, L., Davis, J. R., Trent, J., and Alberts, D. S. Chromosome abnormalities in ovarian adenocarcinoma: I. Nonrandom chromosome abnormalities from 244 cases. Genes Chromosomes Cancer, 25: 290-300, 1999.
56. Hermsen, M. A., Joenje, H., Arwert, F., Welters, M. J., Braakhuis, B. J., Bagnay, M., Westerveld, A., and Slater, R. Centromeric breakage as a major cause of cytogenetic abnormalities in oral squamous cell carcinoma. Genes Chromosomes Cancer, 15: 1-9, 1996.
57. Jin, Y., Martins, C., Jin, C., Salemark, L., Jonsson, N., Persson, B., Roque, L., Fonseca, I., and Wennerberg, J. Nonrandom karyotypic features in squamous cell carcinomas of the skin. Genes Chromosomes Cancer, 26: 295-303, 1999.
58. Sawyer, J. R., Lukacs, J. L., Thomas, E. L., Swanson, C. M., Goosen, L. S., Sammartino, G., Gilliland, J. C., Munshi, N. C., Tricot, G., Shaughnessy, J. D., Jr., and Barlogie, B. Multicolour spectral karyotyping identifies new translocations and a recurring pathway for chromosome loss in multiple myeloma. Br. J. Haematol., 112: 167-174, 2001.
59. Beheshti, B., Park, P. C., Sweet, J. M., Trachtenberg, J., Jewett, M. A., and Squire, J. A. Evidence of chromosomal instability in prostate cancer determined by spectral karyotyping (SKY) and interphase fish analysis. Neoplasia, 3: 62-69, 2001.
60. Richardson, C., and Jasin, M. Frequent chromosomal translocations induced by DNA double-strand breaks. Nature (Lond.), 405: 697-700, 2000.
61. McClintock, B. The stability of broken ends of chromosomes in Zea mays. Genetics, 26: 234-282, 1940.
62. Gisselsson, D., Pettersson, L., Höglund, M., Heidenblad, M., Gorunova, L., Wiegant, J., Mertens, F., Dal Cin, P., Mitelman, F., and Mandahl, N. Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity. Proc. Natl. Acad. Sci. USA, 97: 5357-5362, 2000.
63. Saunders, W. S., Shuster, M., Huang, X., Gharaibeh, B., Enyenihi, A. H., Petersen, I., and Gollin, S. M. Chromosomal instability and cytoskeletal defects in oral cancer cells. Proc. Natl. Acad. Sci. USA, 97: 303-308, 2000.
64. Artandi, S. E., and DePinho, R. A. A critical role for telomeres in suppressing and facilitating carcinogenesis. Curr. Opin. Genet. Dev., 10: 39-46, 2000.
65. Rudolph, K. L., Millard, M., Bosenberg, M. W., and DePinho, R. A. Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nat. Genet., 28: 155-159, 2001.
66. Artandi, S. E., Chang, S., Lee, S. L., Alson, S., Gottlieb, G. J., Chin, L., and DePinho, R. A. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature (Lond.), 406: 641-645, 2000.
67. Gisselsson, D., Jonson, T., Petersen, A., Strombeck, B., Dal Cin, P., Hoglund, M., Mitelman, F., Mertens, F., and Mandahl, N. Telomere dysfunction triggers extensive DNA fragmentation and evolution of complex chromosome abnormalities in human malignant tumors. Proc. Natl. Acad. Sci. USA, 98: 12683-12688, 2001.
68. Myung, K., Chen, C., and Kolodner, R. D. Multiple pathways cooperate in the suppression of genome instability in Saccharomyces cerevisiae. Nature (Lond.), 411: 1073-1076, 2001.
69. Myung, K., Datta, A., and Kolodner, R. D. Suppression of spontaneous chromosomal rearrangements by S phase checkpoint functions in Saccharomyces cerevisiae. Cell, 104: 397-408, 2001.
70. Lo, A. W., Sprung, C. N., Fouladi, B., Pedram, M., Sabatier, L., Ricoul, M., Reynolds, G. E., and Murnane, J. P. Chromosome instability as a result of double-strand breaks near telomeres in mouse embryonic stem cells. Mol. Cell. Biol., 22: 4836-4850, 2002.
71. Narayan, A., Ji, W., Zhang, X. Y., Marrogi, A., Graff, J. R., Baylin, S. B., and Ehrlich, M. Hypomethylation of pericentromeric DNA in breast adenocarcinomas. Int. J. Cancer, 77: 833-838, 1998.
72. Qu, G., Dubeau, L., Narayan, A., Yu, M. C., and Ehrlich, M. Satellite DNA hypomethylation vs. overall genomic hypomethylation in ovarian epithelial tumors of different malignant potential. Mutat. Res., 423: 91-101, 1999.
73. Eden, A., Gaudet, F., Waghmare, A., and Jaenisch, R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science (Wash. DC), 300: 455, 2003.
74. Eichler, E. E. Masquerading repeats: paralogous pitfalls of the human genome. Genome Res., 8: 758-762, 1998.
75. Bailey, J. A., Yavor, A. M., Massa, H. F., Trask, B. J., and Eichler, E. E. Segmental duplications: organization and impact within the current human genome project assembly. Genome Res., 11: 1005-1017, 2001.
76. Horvath, J. E., Bailey, J. A., Locke, D. P., and Eichler, E. E. Lessons from the human genome: transitions between euchromatin and heterochromatin. Hum. Mol. Genet., 10: 2215-2223, 2001.