Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1997 Mar;150(3):901–910.

HMGI(Y) activation by chromosome 6p21 rearrangements in multilineage mesenchymal cells from pulmonary hamartoma.

S Xiao 1, M L Lux 1, R Reeves 1, T J Hudson 1, J A Fletcher 1
PMCID: PMC1857887  PMID: 9060828

Abstract

The chromosome band 6p21 high-mobility group gene, HMGI(Y), encodes DNA-binding proteins with both chromatin structural and gene regulatory roles. Although HMGI(Y) expression is associated with neoplastic transformation, no oncogenic HMGI(Y) mutations have been identified. We report pulmonary chondroid hamartoma chromosome 6p21 aberrations targeting HMGI(Y). Several pulmonary chondroid hamartomas had chromosome rearrangements mapping within 100 kb of HMGI(Y), and one pulmonary chondroid hamartoma contained an intragenic fusion juxtaposing HMGI(Y) A.T book DNA-binding domains with a laminin alpha 4 chain epidermal-growth-factor-like/ zinc-finger-like motif. These findings demonstrate an oncogenic role for HMGI(Y) and for laminin chain transcriptional regulatory motifs.

Full text

PDF
901

Images in this article

904Figure 1
on p.904
906Figure 4
on p.906
907Figure 5
on p.907

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Airenne T., Haakana H., Sainio K., Kallunki T., Kallunki P., Sariola H., Tryggvason K. Structure of the human laminin gamma 2 chain gene (LAMC2): alternative splicing with different tissue distribution of two transcripts. Genomics. 1996 Feb 15;32(1):54–64. doi: 10.1006/geno.1996.0076. [DOI] [PubMed] [Google Scholar]
  2. Ancsin J. B., Kisilevsky R. Laminin interactions important for basement membrane assembly are promoted by zinc and implicate laminin zinc finger-like sequences. J Biol Chem. 1996 Mar 22;271(12):6845–6851. doi: 10.1074/jbc.271.12.6845. [DOI] [PubMed] [Google Scholar]
  3. Ashar H. R., Fejzo M. S., Tkachenko A., Zhou X., Fletcher J. A., Weremowicz S., Morton C. C., Chada K. Disruption of the architectural factor HMGI-C: DNA-binding AT hook motifs fused in lipomas to distinct transcriptional regulatory domains. Cell. 1995 Jul 14;82(1):57–65. doi: 10.1016/0092-8674(95)90052-7. [DOI] [PubMed] [Google Scholar]
  4. Bateson E. M. So-called hamartoma of the lung--a true neoplasm of fibrous connective tissue of the bronchi. Cancer. 1973 Jun;31(6):1458–1467. doi: 10.1002/1097-0142(197306)31:6<1458::aid-cncr2820310622>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  5. Bussemakers M. J., van de Ven W. J., Debruyne F. M., Schalken J. A. Identification of high mobility group protein I(Y) as potential progression marker for prostate cancer by differential hybridization analysis. Cancer Res. 1991 Jan 15;51(2):606–611. [PubMed] [Google Scholar]
  6. Chiappetta G., Bandiera A., Berlingieri M. T., Visconti R., Manfioletti G., Battista S., Martinez-Tello F. J., Santoro M., Giancotti V., Fusco A. The expression of the high mobility group HMGI (Y) proteins correlates with the malignant phenotype of human thyroid neoplasias. Oncogene. 1995 Apr 6;10(7):1307–1314. [PubMed] [Google Scholar]
  7. Dal Cin P., Kools P., De Jonge I., Moerman P., Van de Ven W., Van den Berghe H. Rearrangement of 12q14-15 in pulmonary chondroid hamartoma. Genes Chromosomes Cancer. 1993 Oct;8(2):131–133. doi: 10.1002/gcc.2870080211. [DOI] [PubMed] [Google Scholar]
  8. Davis M., Malcolm S., Rabbitts T. H. Chromosome translocation can occur on either side of the c-myc oncogene in Burkitt lymphoma cells. Nature. 1984 Mar 15;308(5956):286–288. doi: 10.1038/308286a0. [DOI] [PubMed] [Google Scholar]
  9. Disney J. E., Johnson K. R., Magnuson N. S., Sylvester S. R., Reeves R. High-mobility group protein HMG-I localizes to G/Q- and C-bands of human and mouse chromosomes. J Cell Biol. 1989 Nov;109(5):1975–1982. doi: 10.1083/jcb.109.5.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Du W., Maniatis T. The high mobility group protein HMG I(Y) can stimulate or inhibit DNA binding of distinct transcription factor ATF-2 isoforms. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11318–11322. doi: 10.1073/pnas.91.24.11318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Falvo J. V., Thanos D., Maniatis T. Reversal of intrinsic DNA bends in the IFN beta gene enhancer by transcription factors and the architectural protein HMG I(Y). Cell. 1995 Dec 29;83(7):1101–1111. doi: 10.1016/0092-8674(95)90137-x. [DOI] [PubMed] [Google Scholar]
  12. Fedele M., Bandiera A., Chiappetta G., Battista S., Viglietto G., Manfioletti G., Casamassimi A., Santoro M., Giancotti V., Fusco A. Human colorectal carcinomas express high levels of high mobility group HMGI(Y) proteins. Cancer Res. 1996 Apr 15;56(8):1896–1901. [PubMed] [Google Scholar]
  13. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  14. Fletcher J. A., Kozakewich H. P., Hoffer F. A., Lage J. M., Weidner N., Tepper R., Pinkus G. S., Morton C. C., Corson J. M. Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors. N Engl J Med. 1991 Feb 14;324(7):436–442. doi: 10.1056/NEJM199102143240702. [DOI] [PubMed] [Google Scholar]
  15. Fletcher J. A., Longtine J., Wallace K., Mentzer S. J., Sugarbaker D. J. Cytogenetic and histologic findings in 17 pulmonary chondroid hamartomas: evidence for a pathogenetic relationship with lipomas and leiomyomas. Genes Chromosomes Cancer. 1995 Mar;12(3):220–223. doi: 10.1002/gcc.2870120310. [DOI] [PubMed] [Google Scholar]
  16. Fletcher J. A., Pinkus G. S., Donovan K., Naeem R., Sugarbaker D. J., Mentzer S., Pinkus J. L., Longtine J. Clonal rearrangement of chromosome band 6p21 in the mesenchymal component of pulmonary chondroid hamartoma. Cancer Res. 1992 Nov 15;52(22):6224–6228. [PubMed] [Google Scholar]
  17. Fletcher J. A., Pinkus G. S., Weidner N., Morton C. C. Lineage-restricted clonality in biphasic solid tumors. Am J Pathol. 1991 May;138(5):1199–1207. [PMC free article] [PubMed] [Google Scholar]
  18. Friedmann M., Holth L. T., Zoghbi H. Y., Reeves R. Organization, inducible-expression and chromosome localization of the human HMG-I(Y) nonhistone protein gene. Nucleic Acids Res. 1993 Sep 11;21(18):4259–4267. doi: 10.1093/nar/21.18.4259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Frohman M. A. Rapid amplification of complementary DNA ends for generation of full-length complementary DNAs: thermal RACE. Methods Enzymol. 1993;218:340–356. doi: 10.1016/0076-6879(93)18026-9. [DOI] [PubMed] [Google Scholar]
  20. Galaktionov K., Lee A. K., Eckstein J., Draetta G., Meckler J., Loda M., Beach D. CDC25 phosphatases as potential human oncogenes. Science. 1995 Sep 15;269(5230):1575–1577. doi: 10.1126/science.7667636. [DOI] [PubMed] [Google Scholar]
  21. Giancotti V., Bandiera A., Ciani L., Santoro D., Crane-Robinson C., Goodwin G. H., Boiocchi M., Dolcetti R., Casetta B. High-mobility-group (HMG) proteins and histone H1 subtypes expression in normal and tumor tissues of mouse. Eur J Biochem. 1993 Apr 15;213(2):825–832. doi: 10.1111/j.1432-1033.1993.tb17825.x. [DOI] [PubMed] [Google Scholar]
  22. Grosschedl R., Giese K., Pagel J. HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. Trends Genet. 1994 Mar;10(3):94–100. doi: 10.1016/0168-9525(94)90232-1. [DOI] [PubMed] [Google Scholar]
  23. Hudson T. J., Stein L. D., Gerety S. S., Ma J., Castle A. B., Silva J., Slonim D. K., Baptista R., Kruglyak L., Xu S. H. An STS-based map of the human genome. Science. 1995 Dec 22;270(5244):1945–1954. doi: 10.1126/science.270.5244.1945. [DOI] [PubMed] [Google Scholar]
  24. Johansson M., Dietrich C., Mandahl N., Hambraeus G., Johansson L., Clausen P. P., Mitelman F., Heim S. Recombinations of chromosomal bands 6p21 and 14q24 characterise pulmonary hamartomas. Br J Cancer. 1993 Jun;67(6):1236–1241. doi: 10.1038/bjc.1993.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Johansson M., Heim S., Mandahl N., Johansson L., Hambraeus G., Mitelman F. t(3;6;14)(p21;p21;q24) as the sole clonal chromosome abnormality in a hamartoma of the lung. Cancer Genet Cytogenet. 1992 Jun;60(2):219–220. doi: 10.1016/0165-4608(92)90026-5. [DOI] [PubMed] [Google Scholar]
  26. Johnson K. R., Disney J. E., Wyatt C. R., Reeves R. Expression of mRNAs encoding mammalian chromosomal proteins HMG-I and HMG-Y during cellular proliferation. Exp Cell Res. 1990 Mar;187(1):69–76. doi: 10.1016/0014-4827(90)90118-t. [DOI] [PubMed] [Google Scholar]
  27. Johnson K. R., Lehn D. A., Reeves R. Alternative processing of mRNAs encoding mammalian chromosomal high-mobility-group proteins HMG-I and HMG-Y. Mol Cell Biol. 1989 May;9(5):2114–2123. doi: 10.1128/mcb.9.5.2114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kazmierczak B., Hennig Y., Wanschura S., Rogalla P., Bartnitzke S., Van de Ven W., Bullerdiek J. Description of a novel fusion transcript between HMGI-C, a gene encoding for a member of the high mobility group proteins, and the mitochondrial aldehyde dehydrogenase gene. Cancer Res. 1995 Dec 15;55(24):6038–6039. [PubMed] [Google Scholar]
  29. Kazmierczak B., Rosigkeit J., Wanschura S., Meyer-Bolte K., Van de Ven W. J., Kayser K., Krieghoff B., Kastendiek H., Bartnitzke S., Bullerdiek J. HMGI-C rearrangements as the molecular basis for the majority of pulmonary chondroid hamartomas: a survey of 30 tumors. Oncogene. 1996 Feb 1;12(3):515–521. [PubMed] [Google Scholar]
  30. Kazmierczak B., Wanschura S., Rosigkeit J., Meyer-Bolte K., Uschinsky K., Haupt R., Schoenmakers E. F., Bartnitzke S., Van de Ven W. J., Bullerdiek J. Molecular characterization of 12q14-15 rearrangements in three pulmonary chondroid hamartomas. Cancer Res. 1995 Jun 15;55(12):2497–2499. [PubMed] [Google Scholar]
  31. Perez-Atayde A. R., Seiler M. W. Pulmonary hamartoma. An ultrastructural study. Cancer. 1984 Feb 1;53(3):485–492. doi: 10.1002/1097-0142(19840201)53:3<485::aid-cncr2820530319>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  32. Rabbitts T. H. Chromosomal translocations in human cancer. Nature. 1994 Nov 10;372(6502):143–149. doi: 10.1038/372143a0. [DOI] [PubMed] [Google Scholar]
  33. Radic M. Z., Saghbini M., Elton T. S., Reeves R., Hamkalo B. A. Hoechst 33258, distamycin A, and high mobility group protein I (HMG-I) compete for binding to mouse satellite DNA. Chromosoma. 1992 Oct;101(10):602–608. doi: 10.1007/BF00360537. [DOI] [PubMed] [Google Scholar]
  34. Ram T. G., Reeves R., Hosick H. L. Elevated high mobility group-I(Y) gene expression is associated with progressive transformation of mouse mammary epithelial cells. Cancer Res. 1993 Jun 1;53(11):2655–2660. [PubMed] [Google Scholar]
  35. Reeves R., Nissen M. S. Interaction of high mobility group-I (Y) nonhistone proteins with nucleosome core particles. J Biol Chem. 1993 Oct 5;268(28):21137–21146. [PubMed] [Google Scholar]
  36. Reeves R., Nissen M. S. The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. J Biol Chem. 1990 May 25;265(15):8573–8582. [PubMed] [Google Scholar]
  37. Rowley J. D. Biological implications of consistent chromosome rearrangements in leukemia and lymphoma. Cancer Res. 1984 Aug;44(8):3159–3168. [PubMed] [Google Scholar]
  38. Saitoh Y., Laemmli U. K. Metaphase chromosome structure: bands arise from a differential folding path of the highly AT-rich scaffold. Cell. 1994 Feb 25;76(4):609–622. doi: 10.1016/0092-8674(94)90502-9. [DOI] [PubMed] [Google Scholar]
  39. Salminen U. S. Pulmonary hamartoma. A clinical study of 77 cases in a 21-year period and review of literature. Eur J Cardiothorac Surg. 1990;4(1):15–18. doi: 10.1016/1010-7940(90)90234-q. [DOI] [PubMed] [Google Scholar]
  40. Schoenmakers E. F., Wanschura S., Mols R., Bullerdiek J., Van den Berghe H., Van de Ven W. J. Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours. Nat Genet. 1995 Aug;10(4):436–444. doi: 10.1038/ng0895-436. [DOI] [PubMed] [Google Scholar]
  41. Tamimi Y., van der Poel H. G., Denyn M. M., Umbas R., Karthaus H. F., Debruyne F. M., Schalken J. A. Increased expression of high mobility group protein I(Y) in high grade prostatic cancer determined by in situ hybridization. Cancer Res. 1993 Nov 15;53(22):5512–5516. [PubMed] [Google Scholar]
  42. Thanos D., Maniatis T. NF-kappa B: a lesson in family values. Cell. 1995 Feb 24;80(4):529–532. doi: 10.1016/0092-8674(95)90506-5. [DOI] [PubMed] [Google Scholar]
  43. Thanos D., Maniatis T. The high mobility group protein HMG I(Y) is required for NF-kappa B-dependent virus induction of the human IFN-beta gene. Cell. 1992 Nov 27;71(5):777–789. doi: 10.1016/0092-8674(92)90554-p. [DOI] [PubMed] [Google Scholar]
  44. Thanos D., Maniatis T. Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell. 1995 Dec 29;83(7):1091–1100. doi: 10.1016/0092-8674(95)90136-1. [DOI] [PubMed] [Google Scholar]
  45. Tkachuk D. C., Kohler S., Cleary M. L. Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell. 1992 Nov 13;71(4):691–700. doi: 10.1016/0092-8674(92)90602-9. [DOI] [PubMed] [Google Scholar]
  46. Walter M. A., Spillett D. J., Thomas P., Weissenbach J., Goodfellow P. N. A method for constructing radiation hybrid maps of whole genomes. Nat Genet. 1994 May;7(1):22–28. doi: 10.1038/ng0594-22. [DOI] [PubMed] [Google Scholar]
  47. Whitley M. Z., Thanos D., Read M. A., Maniatis T., Collins T. A striking similarity in the organization of the E-selectin and beta interferon gene promoters. Mol Cell Biol. 1994 Oct;14(10):6464–6475. doi: 10.1128/mcb.14.10.6464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Williams A. J., Powell W. L., Collins T., Morton C. C. HMGI(Y) expression in human uterine leiomyomata. Involvement of another high-mobility group architectural factor in a benign neoplasm. Am J Pathol. 1997 Mar;150(3):911–918. [PMC free article] [PubMed] [Google Scholar]
  49. Wood L. D., Farmer A. A., Richmond A. HMGI(Y) and Sp1 in addition to NF-kappa B regulate transcription of the MGSA/GRO alpha gene. Nucleic Acids Res. 1995 Oct 25;23(20):4210–4219. doi: 10.1093/nar/23.20.4210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Xiao S., Renshaw A., Cibas E. S., Hudson T. J., Fletcher J. A. Novel fluorescence in situ hybridization approaches in solid tumors. Characterization of frozen specimens, touch preparations, and cytological preparations. Am J Pathol. 1995 Oct;147(4):896–904. [PMC free article] [PubMed] [Google Scholar]
  51. Zeleznik-Le N. J., Harden A. M., Rowley J. D. 11q23 translocations split the "AT-hook" cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10610–10614. doi: 10.1073/pnas.91.22.10610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. van den Bosch J. M., Wagenaar S. S., Corrin B., Elbers J. R., Knaepen P. J., Westermann C. J. Mesenchymoma of the lung (so called hamartoma): a review of 154 parenchymal and endobronchial cases. Thorax. 1987 Oct;42(10):790–793. doi: 10.1136/thx.42.10.790. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES