Supplemental Table S1. Studies Suggesting 11Q23 Contains a Human Tumor Suppressor Gene(S)

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Supplemental Table S1. Studies Suggesting 11q23 Contains a Human Tumor Suppressor Gene(s)

A. Studies Demonstrating LOH of 11q23

Bethwaite, P.B., Koreth, J., Herrington, C.S., and McGee, J.O. (1995). Loss of heterozygosity occurs at the D11S29 locus on chromosome 11q23 in invasive cervical carcinoma. Br. J. Cancer 71, 814–818.

Dahiya, R., McCarville, J., Lee, C., Hu, W., Kaur, G., Carroll, P., and Deng, G. (1997). Deletion of chromosome 11p15, p12, q22, q23-24 loci in human prostate cancer. Int. J. Cancer 72, 283–288.

Evans, M.F., Koreth, J., Bakkenist, C.J., Herrington, C.S., and McGee, J.O. (1998). Allelic deletion at 11q23.3-q25 is an early event in cervical neoplasia. Oncogene 16, 2557–2564.

Foulkes, W.D., Campbell, I.G., Stamp, G.W., and Trowsdale, J. (1993). Loss of heterozygosity and amplification on chromosome 11q in human ovarian cancer. Br. J. Cancer 67, 268–273.

Gabra, H., Taylor, L., Cohen, B.B., Lessels, A., Eccles, D.M., Leonard, R.C., Smyth, J.F., and Steel, C.M. (1995). Chromosome 11 allele imbalance and clinicopathological correlates in ovarian tumours. Br. J. Cancer 72, 367–375.

Gabra, H., Watson, J.E., Taylor, K.J., Mackay, J., Leonard, R.C., Steel, C.M., Porteous, D.J., and Smyth, J.F. (1996). Definition and refinement of a region of loss of heterozygosity at 11q23.3-q24.3 in epithelial ovarian cancer associated with poor prognosis. Cancer Res. 56, 950–954.

Guo, C., White, P.S., Hogarty, M.D., Brodeur, G.M., Gerbing, R., Stram, D.O., and Maris, J.M. (2000). Deletion of 11q23 is a frequent event in the evolution of MYCN single-copy high-risk neuroblastomas. Med. Pediatr. Oncol. 35, 544–546.

Haidar, M.A., Kantarjian, H., Manshouri, T., Chang, C.Y., O'Brien, S., Freireich, E., Keating, M., and Albitar, M. (2000). ATM gene deletion in patients with adult acute lymphoblastic leukemia. Cancer 88, 1057–1062.

Hampton, G.M., Mannermaa, A., Winquist, R., Alavaikko, M., Blanco, G., Taskinen, P.J., Kiviniemi, H., Newsham, I., Cavenee, W.K., and Evans, G.A. (1994). Loss of heterozygosity in sporadic human breast carcinoma: a common region between 11q22 and 11q23.3. Cancer Res. 54, 4586–4589.

Herbst, R.A., Gutzmer, R., Matiaske, F., Mommert, S., Casper, U., Kapp, A., and Weiss, J. (1999). Identification of two distinct deletion targets at 11q23 in cutaneous malignant melanoma. Int. J. Cancer 80, 205–209.

Herbst, R.A., Larson, A., Weiss, J., Cavenee, W.K., Hampton, G.M., and Arden, K.C. (1995). A defined region of loss of heterozygosity at 11q23 in cutaneous malignant melanoma. Cancer Res. 55, 2494–2496.

Hoang, M.P., Maitra, A., Gazdar, A.F., and Albores-Saavedra, J. (2001). Primary mammary small-cell carcinoma: a molecular analysis of 2 cases. Hum. Pathol. 32, 753–757

Huettner, P.C., Gerhard, D.S., Li, L., Gersell, D.J., Dunnigan, K., Kamarasova, T., and Rader, J.S. (1998). Loss of heterozygosity in clinical stage IB cervical carcinoma: relationship with clinical and histopathologic features. Hum. Pathol. 29, 364–370.

Kersemaekers, A.M., Hermans, J., Fleuren, G.J., and van de Vijver, M.J. (1998a). Loss of heterozygosity for defined regions on chromosomes 3, 11 and 17 in carcinomas of the uterine cervix. Br. J. Cancer 77, 192–200.

Kersemaekers, A.M., Kenter, G.G., Hermans, J., Fleuren, G.J., and van de Vijver, M.J. (1998b). Allelic loss and prognosis in carcinoma of the uterine cervix. Int. J. Cancer 79, 411–417.

Koreth, J., Bakkenist, C.J., and McGee, J.O. (1997). Allelic deletions at chromosome 11q22-q23.1 and 11q25-qterm are frequent in sporadic breast but not colorectal cancers. Oncogene 14, 431–437.

Koreth, J., Bethwaite, P.B., and McGee, J.O. (1995). Mutation at chromosome 11q23 in human non-familial breast cancer: a microdissection microsatellite analysis. J. Pathol. 176, 11–18.

Launonen, V., Stenback, F., Puistola, U., Bloigu, R., Huusko, P., Kytola, S., Kauppila, A., and Winqvist, R. (1998). Chromosome 11q22.3-q25 LOH in ovarian cancer: association with a more aggressive disease course and involved subregions. Gynecol. Oncol. 71, 299–304.

Lazar, A.D., Winter, M.R., Nogueira, C.P., Larson, P.S., Finnemore, E.M., Dolan, R.W., Fuleihan, N., Chakravarti, A., Zietman, A., and Rosenberg, C.L. (1998). Loss of heterozygosity at 11q23 in squamous cell carcinoma of the head and neck is associated with recurrent disease. Clin. Cancer Res. 4, 2787–2793.

Lee, A.S., Seo, Y.C., Chang, A., Tohari, S., Eu, K.W., Seow-Choen, F., and McGee, J.O. (2000). Detailed deletion mapping at chromosome 11q23 in colorectal carcinoma. Br. J. Cancer 83, 750–755.

Maris, J.M., and Matthay, K.K. (1999). Molecular biology of neuroblastoma. J. Clin. Oncol. 17, 2264–2279.

Mora, J., Gerald, W.L., Qin, J., and Cheung, N.K. (2002). Evolving significance of prognostic markers associated with treatment improvement in patients with stage 4 neuroblastoma. Cancer 94, 2756–2765.

Oriola, J., Halperin, I., Mallofre, C., Muntane, J., Angel, M., and Rivera-Fillat, F. (2001). Screening of selected genomic areas potentially involved in thyroid neoplasms. Eur. J. Cancer 37, 2470–2474.

Osborne, R.J., and Hamshere, M.G. (2000). A genome-wide map showing common regions of loss of heterozygosity/allelic imbalance in breast cancer. Cancer Res. 60, 3706–3712.

Rasio, D., Negrini, M., Manenti, G., Dragani, T.A., and Croce, C.M. (1995). Loss of heterozygosity at chromosome 11q in lung adenocarcinoma: identification of three independent regions. Cancer Res. 55, 3988–3991.

Sheu, J.C., Lin, Y.W., Chou, H.C., Huang, G.T., Lee, H.S., Lin, Y.H., Huang, S.Y., Chen, C.H., Wang, J.T., Lee, P.H., et al. (1999). Loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in Taiwan. Br. J. Cancer 80, 468–476.

Tomlinson, I.P., Beck, N.E., and Bodmer, W.F. (1996). Allele loss on chromosome 11q and microsatellite instability in malignant melanoma. Eur. J. Cancer 32A, 1797–1802.

Tomlinson, I.P., and Bodmer, W.F. (1996). Chromosome 11q in sporadic colorectal carcinoma: patterns of allele loss and their significance for tumorigenesis. J. Clin. Pathol. 49, 386–390.

Tomlinson, I.P., Gammack, A.J., Stickland, J.E., Mann, G.J., MacKie, R.M., Kefford, R.F., and McGee, J.O. (1993). Loss of heterozygosity in malignant melanoma at loci on chromosome 11 and 17 implicated in the pathogenesis of other cancers. Genes Chromosomes Cancer 7, 169–172.

Tomlinson, I.P., Strickland, J.E., Lee, A.S., Bromley, L., Evans, M.F., Morton, J., and McGee, J.O. (1995). Loss of heterozygosity on chromosome 11 q in breast cancer. J. Clin. Pathol. 48, 424–428.

Winqvist, R., Hampton, G.M., Mannermaa, A., Blanco, G., Alavaikko, M., Kiviniemi, H., Taskinen, P.J., Evans, G.A., Wright, F.A., Newsham, I., et al. (1995). Loss of heterozygosity for chromosome 11 in primary human breast tumors is associated with poor survival after metastasis. Cancer Res. 55, 2660–2664.

B. Studies Demonstrating LOH of 11q23 with No ATM Mutation

Koike, M., Takeuchi, S., Park, S., Hatta, Y., Yokota, J., Tsuruoka, N., and Koeffler, H.P. (1999). Ovarian cancer: loss of heterozygosity frequently occurs in the ATM gene, but structural alterations do not occur in this gene. Oncology 56, 160–163.

Vorechovsky, I., Rasio, D., Luo, L., Monaco, C., Hammarstrom, L., Webster, A.D., Zaloudik, J., Barbanti-Brodani, G., James, M., Russo, G., et al. (1996). The ATM gene and susceptibility to breast cancer: analysis of 38 breast tumors reveals no evidence for mutation. Cancer Res. 56, 2726–2732.

C. Studies Demonstrating LOH of an 11q23 Subregion Containing the H2AFX Locus but not ATM

Goldberg, E.K., Glendening, J.M., Karanjawala, Z., Sridhar, A., Walker, G.J., Hayward, N.K., Rice, A.J., Kurera, D., Tebha, Y., and Fountain, J.W. (2000). Localization of multiple melanoma tumor-suppressor genes on chromosome 11 by use of homozygosity mapping-of-deletions analysis. Am. J. Hum. Genet. 67, 417–431.

Guo, C., White, P.S., Weiss, M.J., Hogarty, M.D., Thompson, P.M., Stram, D.O., Gerbing, R., Matthay, K.K., Seeger, R.C., Brodeur, G.M., and Maris, J.M. (1999). Allelic deletion at 11q23 is common in MYCN single copy neuroblastomas. Oncogene 18, 4948–4957.

Launonen, V., Mannermaa, A., Stenback, F., Kosma, V.M., Puistola, U., Huusko, P., Anttila, M., Bloigu, R., Saarikoski, S., Kauppila, A., and Winqvist, R. (2000). Loss of heterozygosity at chromosomes 3, 6, 8, 11, 16, and 17 in ovarian cancer: correlation to clinicopathological variables. Cancer Genet. Cytogenet. 122, 49–54.

Mugica-Van Herckenrode, C., Rodriguez, J.A., Iriarte-Campo, V., Carracedo, A., and Barros, F. (1999). Definition of a region of loss of heterozygosity at chromosome 11q in cervical carcinoma. Diagn. Mol. Pathol. 8, 92–96.

O'Sullivan, M.J., Rader, J.S., Gerhard, D.S., Li, Y., Trinkaus, K.M., Gersell, D.J., and Huettner, P.C. (2001). Loss of heterozygosity at 11q23.3 in vasculoinvasive and metastatic squamous cell carcinoma of the cervix. Hum. Pathol. 32, 475–478.

Petzmann, S., Ullmann, R., Klemen, H., Renner, H., and Popper, H.H. (2001). Loss of heterozygosity on chromosome arm 11q in lung carcinoids. Hum. Pathol. 32, 333–338.

Takeuchi, S., Cho, S.K., Seriu, T., Koike, M., Bartram, C.R., Reiter, A., Schrappe, M., Takeuchi, C., Taguchi, H., and Koeffler, H.P. (1999). Identification of three distinct regions of deletion on the long arm of chromosome 11 in childhood acute lymphoblastic leukemia. Oncogene 18, 7387–7388.

Uzawa, K., Suzuki, H., Komiya, A., Nakanishi, H., Ogawara, K., Tanzawa, H., and Sato, K. (1996). Evidence for two distinct tumor-suppressor gene loci on the long arm of chromosome 11 in human oral cancer. Int. J. Cancer 67, 510–514.

D. Studies Demonstrating Deletions of 11q23

Cortes, J., O'Brien, S., Kantarjian, H., Cork, A., Stass, S., Freireich, E.J., Keating, M., Pierce, S., and Estey, E. (1994). Abnormalities in the long arm of chromosome 11 (11q) in patients with de novo and secondary acute myelogenous leukemias and myelodysplastic syndromes. Leukemia 8, 2174–2178.

Dent, J., Hall, G.D., Wilkinson, N., Perren, T.J., Richmond, I., Markham, A.F., Murphy, H., and Bell, S.M. (2003). Cytogenetic alterations in ovarian clear cell carcinoma detected by comparative genomic hybridisation. Br. J. Cancer 88, 1578–1583.

Doneda, L., Montillo, M., Intropido, L., Tedeschi, A., Morra, E., and Larizza, L. (2003). Interphase fluorescence in situ hybridization analysis of del(11)(q23) and del(17)(p13) in chronic lymphocytic leukemia. a study of 40 early-onset patients. Cancer Genet. Cytogenet. 140, 31–36.

Fu, J.F., Hsu, J.J., Tang, T.C., and Shih, L.Y. (2003). Identification of CBL, a proto-oncogene at 11q23.3, as a novel MLL fusion partner in a patient with de novo acute myeloid leukemia. Genes Chromosomes Cancer 37, 214–219.

Granzen, B., Bernhard, B., Reinisch, I., Skopnik, H., and Mertens, R. (1998). Transient myeloproliferative disorder with 11q23 aberration in two neonates with Down syndrome. Ann. Hematol. 77, 51–54.

Hannen, E.J., Bulten, J., Festen, J., Wienk, S.M., and de Wilde, P.C. (2000). Polymorphous low grade adenocarcinoma with distant metastases and deletions on chromosome 6q23-qter and 11q23-qter: a case report. J. Clin. Pathol. 53, 942–945.

Hemmer, S., Wasenius, V.M., Haglund, C., Zhu, Y., Knuutila, S., Franssila, K., and Joensuu, H. (2001). Deletion of 11q23 and cyclin D1 overexpression are frequent aberrations in parathyroid adenomas. Am. J. Pathol. 158, 1355–1362.

Johansson, B., Mertens, F., and Mitelman, F. (1993). Cytogenetic deletion maps of hematologic neoplasms: circumstantial evidence for tumor suppressor loci. Genes Chromosomes Cancer 8, 205–218.

Keldysh, P.L., Dragani, T.A., Fleischman, E.W., Konstantinova, L.N., Perevoschikov, A.G., Pierotti, M.A., Della Porta, G., and Kopnin, B.P. (1993). 11q deletions in human colorectal carcinomas: cytogenetics and restriction fragment length polymorphism analysis. Genes Chromosomes Cancer 6, 45–50.

Knuutila, S., Aalto, Y., Autio, K., Bjorkqvist, A.M., El-Rifai, W., Hemmer, S., Huhta, T., Kettunen, E., Kiuru-Kuhlefelt, S., Larramendy, M.L., et al. (1999). DNA copy number losses in human neoplasms. Am. J. Pathol. 155, 683–694.

Koiffmann, C.P., Gonzalez, C.H., Vianna-Morgante, A.M., Kim, C.A., Odone-Filho, V., and Wajntal, A. (1995). Neuroblastoma in a boy with MCA/MR syndrome, deletion 11q, and duplication 12q. Am. J. Med. Genet. 58, 46–49.

Leblanc, T., Le Coniat, M., Flexor, M., Baruchel, A., Daniel, M.T., and Berger, R. (1996). An interstitial 11q23 deletion proven to be a rearrangement interrupting the MLL gene in an infant with acute myeloblastic leukemia. Leukemia 10, 1844–1846.

Lens, D., Matutes, E., Catovsky, D., and Coignet, L.J. (2000). Frequent deletions at 11q23 and 13q14 in B cell prolymphocytic leukemia (B-PLL). Leukemia 14, 427–430.

Morse, H.G., Gonzalez, R., Moore, G.E., and Robinson, W.A. (1992). Preferential chromosome 11q and/or 17q aberrations in short-term cultures of metastatic melanoma in resections from human brain. Cancer Genet. Cytogenet. 64, 118–126.

Nanjangud, G., Rao, P.H., Hegde, A., Teruya-Feldstein, J., Donnelly, G., Qin, J., Jhanwar, S.C., Zelenetz, A.D., and Chaganti, R.S. (2002). Spectral karyotyping identifies new rearrangements, translocations, and clinical associations in diffuse large B-cell lymphoma. Blood 99, 2554–2561.

Palanisamy, N., Abou-Elella, A.A., Chaganti, S.R., Houldsworth, J., Offit, K., Louie, D.C., Terayu-Feldstein, J., Cigudosa, J.C., Rao, P.H., Sanger, W.G., et al. (2002). Similar patterns of genomic alterations characterize primary mediastinal large-B-cell lymphoma and diffuse large-B-cell lymphoma. Genes Chromosomes Cancer 33, 114–122.

Pulido, H.A., Fakruddin, M.J., Chatterjee, A., Esplin, E.D., Beleno, N., Martinez, G., Posso, H., Evans, G.A., and Murty, V.V. (2000). Identification of a 6-cM minimal deletion at 11q23.1-23.2 and exclusion of PPP2R1B gene as a deletion target in cervical cancer. Cancer Res. 60, 6677–6682.

Raimondi, S.C., Frestedt, J.L., Pui, C.H., Downing, J.R., Head, D.R., Kersey, J.H., and Behm, F.G. (1995). Acute lymphoblastic leukemias with deletion of 11q23 or a novel inversion (11)(p13q23) lack MLL gene rearrangements and have favorable clinical features. Blood 86, 1881–1886.

Rickert, C.H., Simon, R., Bergmann, M., Dockhorn-Dworniczak, B., and Paulus, W. (2000). Comparative genomic hybridization in pineal germ cell tumors. J. Neuropathol. Exp. Neurol. 59, 815–821.

Sanford, J.P., Sait, S.N., Pan, L., Nowak, N.J., Gill, H.J., Le Beau, M.M., Diaz, M.O., Zabel, B., and Shows, T.B. (1993). Characterization of two 11q23.3-11q24 deletions and mapping of associated anonymous DNA markers. Genes Chromosomes Cancer 7, 67–73.

Stilgenbauer, S., Liebisch, P., James, M.R., Schroder, M., Schlegelberger, B., Fischer, K., Bentz, M., Lichter, P., and Dohner, H. (1996). Molecular cytogenetic delineation of a novel critical genomic region in chromosome bands 11q22.3-923.1 in lymphoproliferative disorders. Proc. Natl. Acad. Sci. USA 93, 11837–11841.

Tarkkanen, M., Huuhtanen, R., Virolainen, M., Wiklund, T., Asko-Seljavaara, S., Tukiainen, E., Lepantalo, M., Elomaa, I., and Knuutila, S. (1999). Comparison of genetic changes in primary sarcomas and their pulmonary metastases. Genes Chromosomes Cancer 25, 323–331.

Tomlinson, I.P., and Bodmer, W.F. (1996). Chromosome 11q in sporadic colorectal carcinoma: patterns of allele loss and their significance for tumorigenesis. J. Clin. Pathol. 49, 386–390.

Wang, S.S., Virmani, A., Gazdar, A.F., Minna, J.D., and Evans, G.A. (1999). Refined mapping of two regions of loss of heterozygosity on chromosome band 11q23 in lung cancer. Genes Chromosomes Cancer 25, 154–159.

Zhu, Y., Monni, O., El-Rifai, W., Siitonen, S.M., Vilpo, L., Vilpo, J., and Knuutila, S. (1999). Discontinuous deletions at 11q23 in B cell chronic lymphocytic leukemia. Leukemia 13, 708–712.

Zimonjic, D.B., Keck, C.L., Thorgeirsson, S.S., and Popescu, N.C. (1999). Novel recurrent genetic imbalances in human hepatocellular carcinoma cell lines identified by comparative genomic hybridization. Hepatology 29, 1208–1214.

E. Studies Demonstrating Deletions of 11q23 Regions Containing the H2AFX Locus but Not ATM

Cherif, D., Bernard, O., Paulien, S., James, M.R., Le Paslier, D., and Berger, R. (1994). Hunting 11q23 deletions with fluorescence in situ hybridization (FISH). Leukemia 8, 578–586.

Kobayashi, H., Espinosa, R., 3rd, Fernald, A.A., Begy, C., Diaz, M.O., Le Beau, M.M., and Rowley, J.D. (1993). Analysis of deletions of the long arm of chromosome 11 in hematologic malignancies with fluorescence in situ hybridization. Genes Chromosomes Cancer 8, 246–252.

Tomlinson, I.P., Nicolai, H., Solomon, E., and Bodmer, W.F. (1996). The frequency and mechanism of loss of heterozygosity on chromosome 11q in breast cancer. J. Pathol. 180, 38–43.

F. Study Demonstrating Deletions Associated with LOH of ATM Often Delete the H2AFX Locus

Stilgenbauer, S., Winkler, D., Ott, G., Schaffner, C., Leupolt, E., Bentz, M., Moller, P., Muller-Hermelink, H.K., James, M.R., Lichter, P., and Dohner, H. (1999). Molecular characterization of 11q deletions points to a pathogenic role of the ATM gene in mantle cell lymphoma. Blood 94, 3262–3264.