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. 1998 Aug;78(4):495–503. doi: 10.1038/bjc.1998.521

Molecular characterization of a novel amplicon at 1q21-q22 frequently observed in human sarcomas.

A Forus 1, J M Berner 1, L A Meza-Zepeda 1, G Saeter 1, D Mischke 1, O Fodstad 1, O Myklebost 1
PMCID: PMC2063085  PMID: 9716033

Abstract

In a recent comparative genomic hybridization (CGH) study of a panel of sarcomas, we detected recurrent amplification of 1q21-q22 in soft tissue and bone tumours. Amplification of this region had not previously been associated with sarcoma development, but occasional amplification of CACY/S100A6 and MUC1 in 1q21 had been reported for melanoma and breast carcinoma respectively. Initial screening by Southern blot analysis showed amplification of S100A6, FLG and SPRR3 in several sarcomas and, in a first attempt to characterize the 1q21-q22 amplicon in more detail, we have now investigated the amplification status of these and 11 other markers in the region in 35 sarcoma samples. FLG was the most frequently amplified gene, and the markers located in the same 4.5-Mb region as FLG showed a higher incidence of amplification than the more distal ones. However, for most of the 14 markers, amplification levels were low, and only APOA2 and the anonymous marker D1S3620 showed high-level amplifications (> tenfold increases) in one sample each. We used fluorescence in situ hybridization (FISH) to determine the amplification patterns of two overlapping yeast artificial chromosomes (YACs) covering the region between D1S3620 and FLG (789f2 and 764a1), as well as two more distally located YACs in nine selected samples. Six samples had amplification of the YAC containing D1S3620 and, in three, 764a1 was also included. Five of these tumours showed normal copies of the more distal YACs; thus, it seems likely that an important gene may be located within 789f2, or very close. Two samples had high copy numbers of the most distal YACs. Taken together, FISH and molecular analyses indicate complex amplification patterns in 1q21-q22 with at least two amplicons: one located near D1S3620/789f2 and one more distal.

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Selected References

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

  1. Albertsen H. M., Abderrahim H., Cann H. M., Dausset J., Le Paslier D., Cohen D. Construction and characterization of a yeast artificial chromosome library containing seven haploid human genome equivalents. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4256–4260. doi: 10.1073/pnas.87.11.4256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alitalo K., Schwab M. Oncogene amplification in tumor cells. Adv Cancer Res. 1986;47:235–281. doi: 10.1016/s0065-230x(08)60201-8. [DOI] [PubMed] [Google Scholar]
  3. Armengol G., Tarkkanen M., Virolainen M., Forus A., Valle J., Böhling T., Asko-Seljavaara S., Blomqvist C., Elomaa I., Karaharju E. Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization. Br J Cancer. 1997;75(10):1403–1409. doi: 10.1038/bjc.1997.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berner J. M., Forus A., Elkahloun A., Meltzer P. S., Fodstad O., Myklebost O. Separate amplified regions encompassing CDK4 and MDM2 in human sarcomas. Genes Chromosomes Cancer. 1996 Dec;17(4):254–259. doi: 10.1002/(SICI)1098-2264(199612)17:4<254::AID-GCC7>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  5. Berner J. M., Meza-Zepeda L. A., Kools P. F., Forus A., Schoenmakers E. F., Van de Ven W. J., Fodstad O., Myklebost O. HMGIC, the gene for an architectural transcription factor, is amplified and rearranged in a subset of human sarcomas. Oncogene. 1997 Jun 19;14(24):2935–2941. doi: 10.1038/sj.onc.1201135. [DOI] [PubMed] [Google Scholar]
  6. Bièche I., Champème M. H., Lidereau R. Loss and gain of distinct regions of chromosome 1q in primary breast cancer. Clin Cancer Res. 1995 Jan;1(1):123–127. [PubMed] [Google Scholar]
  7. Bièche I., Lidereau R. A gene dosage effect is responsible for high overexpression of the MUC1 gene observed in human breast tumors. Cancer Genet Cytogenet. 1997 Oct 1;98(1):75–80. doi: 10.1016/s0165-4608(96)00410-4. [DOI] [PubMed] [Google Scholar]
  8. Dal Cin P., Kools P., Sciot R., De Wever I., Van Damme B., Van de Ven W., Van den Berghe H. Cytogenetic and fluorescence in situ hybridization investigation of ring chromosomes characterizing a specific pathologic subgroup of adipose tissue tumors. Cancer Genet Cytogenet. 1993 Jul 15;68(2):85–90. doi: 10.1016/0165-4608(93)90001-3. [DOI] [PubMed] [Google Scholar]
  9. Dracopoli N. C., Bruns G. A., Brodeur G. M., Landes G. M., Matise T. C., Seldin M. F., Vance J. M., Weith A. Report and abstracts of the First International Workshop on Human Chromosome 1 Mapping 1994. Bethesda, Maryland, March 25-27, 1994. Cytogenet Cell Genet. 1994;67(3):144–165. [PubMed] [Google Scholar]
  10. Eckert R. L., Green H. Structure and evolution of the human involucrin gene. Cell. 1986 Aug 15;46(4):583–589. doi: 10.1016/0092-8674(86)90884-6. [DOI] [PubMed] [Google Scholar]
  11. Forus A., Flørenes V. A., Maelandsmo G. M., Meltzer P. S., Fodstad O., Myklebost O. Mapping of amplification units in the q13-14 region of chromosome 12 in human sarcomas: some amplica do not include MDM2. Cell Growth Differ. 1993 Dec;4(12):1065–1070. [PubMed] [Google Scholar]
  12. Forus A., Weghuis D. O., Smeets D., Fodstad O., Myklebost O., Geurts van Kessel A. Comparative genomic hybridization analysis of human sarcomas: II. Identification of novel amplicons at 6p and 17p in osteosarcomas. Genes Chromosomes Cancer. 1995 Sep;14(1):15–21. doi: 10.1002/gcc.2870140104. [DOI] [PubMed] [Google Scholar]
  13. Forus A., Weghuis D. O., Smeets D., Fodstad O., Myklebost O., van Kessel A. G. Comparative genomic hybridization analysis of human sarcomas: I. Occurrence of genomic imbalances and identification of a novel major amplicon at 1q21-q22 in soft tissue sarcomas. Genes Chromosomes Cancer. 1995 Sep;14(1):8–14. doi: 10.1002/gcc.2870140103. [DOI] [PubMed] [Google Scholar]
  14. Gaudray P., Szepetowski P., Escot C., Birnbaum D., Theillet C. DNA amplification at 11q13 in human cancer: from complexity to perplexity. Mutat Res. 1992 May;276(3):317–328. doi: 10.1016/0165-1110(92)90018-5. [DOI] [PubMed] [Google Scholar]
  15. Gibbs S., Fijneman R., Wiegant J., van Kessel A. G., van De Putte P., Backendorf C. Molecular characterization and evolution of the SPRR family of keratinocyte differentiation markers encoding small proline-rich proteins. Genomics. 1993 Jun;16(3):630–637. doi: 10.1006/geno.1993.1240. [DOI] [PubMed] [Google Scholar]
  16. Heim S., Mandahl N., Kristoffersson U., Mitelman F., Röser B., Rydholm A., Willén H. Marker ring chromosome--a new cytogenetic abnormality characterizing lipogenic tumors? Cancer Genet Cytogenet. 1987 Feb;24(2):319–326. doi: 10.1016/0165-4608(87)90114-2. [DOI] [PubMed] [Google Scholar]
  17. Hohl D., de Viragh P. A., Amiguet-Barras F., Gibbs S., Backendorf C., Huber M. The small proline-rich proteins constitute a multigene family of differentially regulated cornified cell envelope precursor proteins. J Invest Dermatol. 1995 Jun;104(6):902–909. doi: 10.1111/1523-1747.ep12606176. [DOI] [PubMed] [Google Scholar]
  18. Huang L. S., Bock S. C., Feinstein S. I., Breslow J. L. Human apolipoprotein B cDNA clone isolation and demonstration that liver apolipoprotein B mRNA is 22 kilobases in length. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6825–6829. doi: 10.1073/pnas.82.20.6825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kallioniemi A., Kallioniemi O. P., Piper J., Tanner M., Stokke T., Chen L., Smith H. S., Pinkel D., Gray J. W., Waldman F. M. Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2156–2160. doi: 10.1073/pnas.91.6.2156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kallioniemi A., Kallioniemi O. P., Sudar D., Rutovitz D., Gray J. W., Waldman F., Pinkel D. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. 1992 Oct 30;258(5083):818–821. doi: 10.1126/science.1359641. [DOI] [PubMed] [Google Scholar]
  21. Kallioniemi O. P., Kallioniemi A., Piper J., Isola J., Waldman F. M., Gray J. W., Pinkel D. Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors. Genes Chromosomes Cancer. 1994 Aug;10(4):231–243. doi: 10.1002/gcc.2870100403. [DOI] [PubMed] [Google Scholar]
  22. Khatib Z. A., Matsushime H., Valentine M., Shapiro D. N., Sherr C. J., Look A. T. Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas. Cancer Res. 1993 Nov 15;53(22):5535–5541. [PubMed] [Google Scholar]
  23. Kovacs G. Abnormalities of chromosome No. 1 in human solid malignant tumours. Int J Cancer. 1978 Jun 15;21(6):688–694. doi: 10.1002/ijc.2910210604. [DOI] [PubMed] [Google Scholar]
  24. Larramendy M. L., Tarkkanen M., Blomqvist C., Virolainen M., Wiklund T., Asko-Seljavaara S., Elomaa I., Knuutila S. Comparative genomic hybridization of malignant fibrous histiocytoma reveals a novel prognostic marker. Am J Pathol. 1997 Oct;151(4):1153–1161. [PMC free article] [PubMed] [Google Scholar]
  25. Lee S. W., Tomasetto C., Swisshelm K., Keyomarsi K., Sager R. Down-regulation of a member of the S100 gene family in mammary carcinoma cells and reexpression by azadeoxycytidine treatment. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2504–2508. doi: 10.1073/pnas.89.6.2504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Maelandsmo G. M., Berner J. M., Flørenes V. A., Forus A., Hovig E., Fodstad O., Myklebost O. Homozygous deletion frequency and expression levels of the CDKN2 gene in human sarcomas--relationship to amplification and mRNA levels of CDK4 and CCND1. Br J Cancer. 1995 Aug;72(2):393–398. doi: 10.1038/bjc.1995.344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Maelandsmo G. M., Flørenes V. A., Mellingsaeter T., Hovig E., Kerbel R. S., Fodstad O. Differential expression patterns of S100A2, S100A4 and S100A6 during progression of human malignant melanoma. Int J Cancer. 1997 Aug 22;74(4):464–469. doi: 10.1002/(sici)1097-0215(19970822)74:4<464::aid-ijc19>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  28. Marenholz I., Volz A., Ziegler A., Davies A., Ragoussis I., Korge B. P., Mischke D. Genetic analysis of the epidermal differentiation complex (EDC) on human chromosome 1q21: chromosomal orientation, new markers, and a 6-Mb YAC contig. Genomics. 1996 Nov 1;37(3):295–302. doi: 10.1006/geno.1996.0563. [DOI] [PubMed] [Google Scholar]
  29. Muleris M., Almeida A., Gerbault-Seureau M., Malfoy B., Dutrillaux B. Detection of DNA amplification in 17 primary breast carcinomas with homogeneously staining regions by a modified comparative genomic hybridization technique. Genes Chromosomes Cancer. 1994 Jul;10(3):160–170. doi: 10.1002/gcc.2870100303. [DOI] [PubMed] [Google Scholar]
  30. Mäkelä T. P., Kere J., Winqvist R., Alitalo K. Intrachromosomal rearrangements fusing L-myc and rlf in small-cell lung cancer. Mol Cell Biol. 1991 Aug;11(8):4015–4021. doi: 10.1128/mcb.11.8.4015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Nau M. M., Brooks B. J., Battey J., Sausville E., Gazdar A. F., Kirsch I. R., McBride O. W., Bertness V., Hollis G. F., Minna J. D. L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature. 1985 Nov 7;318(6041):69–73. doi: 10.1038/318069a0. [DOI] [PubMed] [Google Scholar]
  32. Nilbert M., Rydholm A., Mitelman F., Meltzer P. S., Mandahl N. Characterization of the 12q13-15 amplicon in soft tissue tumors. Cancer Genet Cytogenet. 1995 Aug;83(1):32–36. doi: 10.1016/s0165-4608(95)00016-x. [DOI] [PubMed] [Google Scholar]
  33. Nilbert M., Rydholm A., Willén H., Mitelman F., Mandahl N. MDM2 gene amplification correlates with ring chromosome in soft tissue tumors. Genes Chromosomes Cancer. 1994 Apr;9(4):261–265. doi: 10.1002/gcc.2870090406. [DOI] [PubMed] [Google Scholar]
  34. Orndal C., Mandahl N., Rydholm A., Willén H., Brosjö O., Heim S., Mitelman F. Supernumerary ring chromosomes in five bone and soft tissue tumors of low or borderline malignancy. Cancer Genet Cytogenet. 1992 Jun;60(2):170–175. doi: 10.1016/0165-4608(92)90011-v. [DOI] [PubMed] [Google Scholar]
  35. Oshimura M., Sonta S., Sandberg A. A. Trisomy of the long arm of chromosome No. 1 in human leukemia. J Natl Cancer Inst. 1976 Jan;56(1):183–184. doi: 10.1093/jnci/56.1.183. [DOI] [PubMed] [Google Scholar]
  36. Pedeutour F., Suijkerbuijk R. F., Forus A., Van Gaal J., Van de Klundert W., Coindre J. M., Nicolo G., Collin F., Van Haelst U., Huffermann K. Complex composition and co-amplification of SAS and MDM2 in ring and giant rod marker chromosomes in well-differentiated liposarcoma. Genes Chromosomes Cancer. 1994 Jun;10(2):85–94. doi: 10.1002/gcc.2870100203. [DOI] [PubMed] [Google Scholar]
  37. Pedeutour F., Suijkerbuijk R. F., Van Gaal J., Van de Klundert W., Coindre J. M., Van Haelst A., Collin F., Huffermann K., Turc-Carel C. Chromosome 12 origin in rings and giant markers in well-differentiated liposarcoma. Cancer Genet Cytogenet. 1993 Apr;66(2):133–134. doi: 10.1016/0165-4608(93)90245-h. [DOI] [PubMed] [Google Scholar]
  38. Presland R. B., Haydock P. V., Fleckman P., Nirunsuksiri W., Dale B. A. Characterization of the human epidermal profilaggrin gene. Genomic organization and identification of an S-100-like calcium binding domain at the amino terminus. J Biol Chem. 1992 Nov 25;267(33):23772–23781. [PubMed] [Google Scholar]
  39. Rogne S., Myklebost O., Høyheim B., Olaisen B., Gedde-Dahl T., Jr The genes for apolipoprotein all (APOA2) and the Duffy blood group (FY) are linked on chromosome 1 in man. Genomics. 1989 Feb;4(2):169–173. doi: 10.1016/0888-7543(89)90296-6. [DOI] [PubMed] [Google Scholar]
  40. Rowley J. D. Mapping of human chromosomal regions related to neoplasia: evidence from chromosomes 1 and 17. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5729–5733. doi: 10.1073/pnas.74.12.5729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Schäfer B. W., Heizmann C. W. The S100 family of EF-hand calcium-binding proteins: functions and pathology. Trends Biochem Sci. 1996 Apr;21(4):134–140. doi: 10.1016/s0968-0004(96)80167-8. [DOI] [PubMed] [Google Scholar]
  42. Schäfer B. W., Wicki R., Engelkamp D., Mattei M. G., Heizmann C. W. Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: rationale for a new nomenclature of the S100 calcium-binding protein family. Genomics. 1995 Feb 10;25(3):638–643. doi: 10.1016/0888-7543(95)80005-7. [DOI] [PubMed] [Google Scholar]
  43. Swallow D. M., Gendler S., Griffiths B., Corney G., Taylor-Papadimitriou J., Bramwell M. E. The human tumour-associated epithelial mucins are coded by an expressed hypervariable gene locus PUM. Nature. 1987 Jul 2;328(6125):82–84. doi: 10.1038/328082a0. [DOI] [PubMed] [Google Scholar]
  44. Szymanska J., Tarkkanen M., Wiklund T., Virolainen M., Blomqvist C., Asko-Seljavaara S., Tukiainen E., Elomaa I., Knuutila S. Gains and losses of DNA sequences in liposarcomas evaluated by comparative genomic hybridization. Genes Chromosomes Cancer. 1996 Feb;15(2):89–94. doi: 10.1002/(SICI)1098-2264(199602)15:2<89::AID-GCC2>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
  45. Szymanska J., Virolainen M., Tarkkanen M., Wiklund T., Asko-Seljavaara S., Tukiainen E., Elomaa I., Blomqvist C., Knuutila S. Overrepresentation of 1q21-23 and 12q13-21 in lipoma-like liposarcomas but not in benign lipomas: a comparative genomic hybridization study. Cancer Genet Cytogenet. 1997 Nov;99(1):14–18. doi: 10.1016/s0165-4608(96)00436-0. [DOI] [PubMed] [Google Scholar]
  46. Tarkkanen M., Karhu R., Kallioniemi A., Elomaa I., Kivioja A. H., Nevalainen J., Böhling T., Karaharju E., Hyytinen E., Knuutila S. Gains and losses of DNA sequences in osteosarcomas by comparative genomic hybridization. Cancer Res. 1995 Mar 15;55(6):1334–1338. [PubMed] [Google Scholar]
  47. Tsarfaty I., Hareuveni M., Horev J., Zaretsky J., Weiss M., Jeltsch J. M., Garnier J. M., Lathe R., Keydar I., Wreschner D. H. Isolation and characterization of an expressed hypervariable gene coding for a breast-cancer-associated antigen. Gene. 1990 Sep 14;93(2):313–318. doi: 10.1016/0378-1119(90)90242-j. [DOI] [PubMed] [Google Scholar]
  48. Tucci A., Goldberger G., Whitehead A. S., Kay R. M., Woods D. E., Colten H. R. Biosynthesis and postsynthetic processing of human C-reactive protein. J Immunol. 1983 Nov;131(5):2416–2419. [PubMed] [Google Scholar]
  49. Weber-Hall S., Anderson J., McManus A., Abe S., Nojima T., Pinkerton R., Pritchard-Jones K., Shipley J. Gains, losses, and amplification of genomic material in rhabdomyosarcoma analyzed by comparative genomic hybridization. Cancer Res. 1996 Jul 15;56(14):3220–3224. [PubMed] [Google Scholar]
  50. Weterman M. A., Stoopen G. M., van Muijen G. N., Kuznicki J., Ruiter D. J., Bloemers H. P. Expression of calcyclin in human melanoma cell lines correlates with metastatic behavior in nude mice. Cancer Res. 1992 Mar 1;52(5):1291–1296. [PubMed] [Google Scholar]
  51. Weterman M. A., Wilbrink M., Dijkhuizen T., van den Berg E., Geurts van Kessel A. Fine mapping of the 1q21 breakpoint of the papillary renal cell carcinoma-associated (X;1) translocation. Hum Genet. 1996 Jul;98(1):16–21. doi: 10.1007/s004390050153. [DOI] [PubMed] [Google Scholar]
  52. Wolf M., Aaltonen L. A., Szymanska J., Tarkkanen M., Blomqvist C., Berner J. M., Myklebost O., Knuutila S. Complexity of 12q13-22 amplicon in liposarcoma: microsatellite repeat analysis. Genes Chromosomes Cancer. 1997 Jan;18(1):66–70. doi: 10.1002/(sici)1098-2264(199701)18:1<66::aid-gcc8>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]

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