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. 1996 Aug 20;93(17):9172–9176. doi: 10.1073/pnas.93.17.9172

Microsatellite instability in childhood rhabdomyosarcoma is locus specific and correlates with fractional allelic loss.

M Visser 1, J Bras 1, C Sijmons 1, P Devilee 1, L C Wijnaendts 1, J C van der Linden 1, P A Voûte 1, F Baas 1
PMCID: PMC38614  PMID: 8799173

Abstract

Replication errors (RERs) were initially identified in hereditary nonpolyposis colon cancer and other tumors of Lynch syndrome II. Mutations in genes involved in mismatch repair give rise to a mutator phenotype, resulting in RERs. The mutator phenotype is thought to predispose to malignant transformation. Here we show that in the embryonal form of childhood rhabdomyosarcoma, RERs also occur, but in contrast to hereditary nonpolyposis colon cancer, only a subset of the microsatellite loci analyzed show RERs. The occurrence of RERs is strongly correlated with increased fractional allelic loss (P < 0.001), suggesting that the occurrence of RERs is a secondary phenomenon in rhabdomyosarcoma. Coincidental loss of genes involved in mismatch repair, possibly due to their proximity to tumor suppressor genes involved in tumor progression of embryonal form of childhood rhabdomyosarcoma, could explain the observed phenomenon.

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Selected References

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

  1. Aaltonen L. A., Peltomäki P., Leach F. S., Sistonen P., Pylkkänen L., Mecklin J. P., Järvinen H., Powell S. M., Jen J., Hamilton S. R. Clues to the pathogenesis of familial colorectal cancer. Science. 1993 May 7;260(5109):812–816. doi: 10.1126/science.8484121. [DOI] [PubMed] [Google Scholar]
  2. Agamanolis D. P., Dasu S., Krill C. E., Jr Tumors of skeletal muscle. Hum Pathol. 1986 Aug;17(8):778–795. doi: 10.1016/s0046-8177(86)80198-8. [DOI] [PubMed] [Google Scholar]
  3. Barr F. G., Galili N., Holick J., Biegel J. A., Rovera G., Emanuel B. S. Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993 Feb;3(2):113–117. doi: 10.1038/ng0293-113. [DOI] [PubMed] [Google Scholar]
  4. Datta A., Jinks-Robertson S. Association of increased spontaneous mutation rates with high levels of transcription in yeast. Science. 1995 Jun 16;268(5217):1616–1619. doi: 10.1126/science.7777859. [DOI] [PubMed] [Google Scholar]
  5. Gaiger A. M., Soule E. H., Newton W. A., Jr Pathology of rhabdomyosarcoma: experience of the Intergroup Rhabdomyosarcoma Study, 1972-78. Natl Cancer Inst Monogr. 1981 Apr;(56):19–27. [PubMed] [Google Scholar]
  6. Galili N., Davis R. J., Fredericks W. J., Mukhopadhyay S., Rauscher F. J., 3rd, Emanuel B. S., Rovera G., Barr F. G. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993 Nov;5(3):230–235. doi: 10.1038/ng1193-230. [DOI] [PubMed] [Google Scholar]
  7. Gibbs M., Collick A., Kelly R. G., Jeffreys A. J. A tetranucleotide repeat mouse minisatellite displaying substantial somatic instability during early preimplantation development. Genomics. 1993 Jul;17(1):121–128. doi: 10.1006/geno.1993.1292. [DOI] [PubMed] [Google Scholar]
  8. Gonzalez-Zulueta M., Ruppert J. M., Tokino K., Tsai Y. C., Spruck C. H., 3rd, Miyao N., Nichols P. W., Hermann G. G., Horn T., Steven K. Microsatellite instability in bladder cancer. Cancer Res. 1993 Dec 1;53(23):5620–5623. [PubMed] [Google Scholar]
  9. Ionov Y., Peinado M. A., Malkhosyan S., Shibata D., Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993 Jun 10;363(6429):558–561. doi: 10.1038/363558a0. [DOI] [PubMed] [Google Scholar]
  10. Koi M., Johnson L. A., Kalikin L. M., Little P. F., Nakamura Y., Feinberg A. P. Tumor cell growth arrest caused by subchromosomal transferable DNA fragments from chromosome 11. Science. 1993 Apr 16;260(5106):361–364. doi: 10.1126/science.8469989. [DOI] [PubMed] [Google Scholar]
  11. Leach F. S., Nicolaides N. C., Papadopoulos N., Liu B., Jen J., Parsons R., Peltomäki P., Sistonen P., Aaltonen L. A., Nyström-Lahti M. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993 Dec 17;75(6):1215–1225. doi: 10.1016/0092-8674(93)90330-s. [DOI] [PubMed] [Google Scholar]
  12. Lindblom A., Tannergård P., Werelius B., Nordenskjöld M. Genetic mapping of a second locus predisposing to hereditary non-polyposis colon cancer. Nat Genet. 1993 Nov;5(3):279–282. doi: 10.1038/ng1193-279. [DOI] [PubMed] [Google Scholar]
  13. Liu B., Nicolaides N. C., Markowitz S., Willson J. K., Parsons R. E., Jen J., Papadopolous N., Peltomäki P., de la Chapelle A., Hamilton S. R. Mismatch repair gene defects in sporadic colorectal cancers with microsatellite instability. Nat Genet. 1995 Jan;9(1):48–55. doi: 10.1038/ng0195-48. [DOI] [PubMed] [Google Scholar]
  14. Loeb L. A., Springgate C. F., Battula N. Errors in DNA replication as a basis of malignant changes. Cancer Res. 1974 Sep;34(9):2311–2321. [PubMed] [Google Scholar]
  15. Loh W. E., Jr, Scrable H. J., Livanos E., Arboleda M. J., Cavenee W. K., Oshimura M., Weissman B. E. Human chromosome 11 contains two different growth suppressor genes for embryonal rhabdomyosarcoma. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1755–1759. doi: 10.1073/pnas.89.5.1755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lothe R. A., Peltomäki P., Meling G. I., Aaltonen L. A., Nyström-Lahti M., Pylkkänen L., Heimdal K., Andersen T. I., Møller P., Rognum T. O. Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res. 1993 Dec 15;53(24):5849–5852. [PubMed] [Google Scholar]
  17. Lynch H. T., Lanspa S., Smyrk T., Boman B., Watson P., Lynch J. Hereditary nonpolyposis colorectal cancer (Lynch syndromes I & II). Genetics, pathology, natural history, and cancer control, Part I. Cancer Genet Cytogenet. 1991 Jun;53(2):143–160. doi: 10.1016/0165-4608(91)90093-a. [DOI] [PubMed] [Google Scholar]
  18. Merlo A., Mabry M., Gabrielson E., Vollmer R., Baylin S. B., Sidransky D. Frequent microsatellite instability in primary small cell lung cancer. Cancer Res. 1994 Apr 15;54(8):2098–2101. [PubMed] [Google Scholar]
  19. Mironov N. M., Aguelon M. A., Potapova G. I., Omori Y., Gorbunov O. V., Klimenkov A. A., Yamasaki H. Alterations of (CA)n DNA repeats and tumor suppressor genes in human gastric cancer. Cancer Res. 1994 Jan 1;54(1):41–44. [PubMed] [Google Scholar]
  20. Modrich P. Mismatch repair, genetic stability, and cancer. Science. 1994 Dec 23;266(5193):1959–1960. doi: 10.1126/science.7801122. [DOI] [PubMed] [Google Scholar]
  21. Nicolaides N. C., Papadopoulos N., Liu B., Wei Y. F., Carter K. C., Ruben S. M., Rosen C. A., Haseltine W. A., Fleischmann R. D., Fraser C. M. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature. 1994 Sep 1;371(6492):75–80. doi: 10.1038/371075a0. [DOI] [PubMed] [Google Scholar]
  22. Papadopoulos N., Nicolaides N. C., Liu B., Parsons R., Lengauer C., Palombo F., D'Arrigo A., Markowitz S., Willson J. K., Kinzler K. W. Mutations of GTBP in genetically unstable cells. Science. 1995 Jun 30;268(5219):1915–1917. doi: 10.1126/science.7604266. [DOI] [PubMed] [Google Scholar]
  23. Papadopoulos N., Nicolaides N. C., Wei Y. F., Ruben S. M., Carter K. C., Rosen C. A., Haseltine W. A., Fleischmann R. D., Fraser C. M., Adams M. D. Mutation of a mutL homolog in hereditary colon cancer. Science. 1994 Mar 18;263(5153):1625–1629. doi: 10.1126/science.8128251. [DOI] [PubMed] [Google Scholar]
  24. Parsons R., Li G. M., Longley M., Modrich P., Liu B., Berk T., Hamilton S. R., Kinzler K. W., Vogelstein B. Mismatch repair deficiency in phenotypically normal human cells. Science. 1995 May 5;268(5211):738–740. doi: 10.1126/science.7632227. [DOI] [PubMed] [Google Scholar]
  25. Risinger J. I., Berchuck A., Kohler M. F., Watson P., Lynch H. T., Boyd J. Genetic instability of microsatellites in endometrial carcinoma. Cancer Res. 1993 Nov 1;53(21):5100–5103. [PubMed] [Google Scholar]
  26. Scrable H. J., Witte D. P., Lampkin B. C., Cavenee W. K. Chromosomal localization of the human rhabdomyosarcoma locus by mitotic recombination mapping. Nature. 1987 Oct 15;329(6140):645–647. doi: 10.1038/329645a0. [DOI] [PubMed] [Google Scholar]
  27. Scrable H., Cavenee W., Ghavimi F., Lovell M., Morgan K., Sapienza C. A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7480–7484. doi: 10.1073/pnas.86.19.7480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Scrable H., Witte D., Shimada H., Seemayer T., Sheng W. W., Soukup S., Koufos A., Houghton P., Lampkin B., Cavenee W. Molecular differential pathology of rhabdomyosarcoma. Genes Chromosomes Cancer. 1989 Sep;1(1):23–35. doi: 10.1002/gcc.2870010106. [DOI] [PubMed] [Google Scholar]
  29. Shibata D., Peinado M. A., Ionov Y., Malkhosyan S., Perucho M. Genomic instability in repeated sequences is an early somatic event in colorectal tumorigenesis that persists after transformation. Nat Genet. 1994 Mar;6(3):273–281. doi: 10.1038/ng0394-273. [DOI] [PubMed] [Google Scholar]
  30. Shridhar V., Siegfried J., Hunt J., del Mar Alonso M., Smith D. I. Genetic instability of microsatellite sequences in many non-small cell lung carcinomas. Cancer Res. 1994 Apr 15;54(8):2084–2087. [PubMed] [Google Scholar]
  31. Thibodeau S. N., Bren G., Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993 May 7;260(5109):816–819. doi: 10.1126/science.8484122. [DOI] [PubMed] [Google Scholar]
  32. Wijnaendts L. C., van der Linden J. C., van Unnik A. J., Delemarre J. F., Voute P. A., Meijer C. J. Histopathological classification of childhood rhabdomyosarcomas: relationship with clinical parameters and prognosis. Hum Pathol. 1994 Sep;25(9):900–907. doi: 10.1016/0046-8177(94)90009-4. [DOI] [PubMed] [Google Scholar]
  33. Wooster R., Cleton-Jansen A. M., Collins N., Mangion J., Cornelis R. S., Cooper C. S., Gusterson B. A., Ponder B. A., von Deimling A., Wiestler O. D. Instability of short tandem repeats (microsatellites) in human cancers. Nat Genet. 1994 Feb;6(2):152–156. doi: 10.1038/ng0294-152. [DOI] [PubMed] [Google Scholar]
  34. Zielenski J., Markiewicz D., Rininsland F., Rommens J., Tsui L. C. A cluster of highly polymorphic dinucleotide repeats in intron 17b of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Am J Hum Genet. 1991 Dec;49(6):1256–1262. [PMC free article] [PubMed] [Google Scholar]
  35. de Wind N., Dekker M., Berns A., Radman M., te Riele H. Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell. 1995 Jul 28;82(2):321–330. doi: 10.1016/0092-8674(95)90319-4. [DOI] [PubMed] [Google Scholar]

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