Loss of heterozygosity at chromosome 9p21 is a frequent finding in enteropathy-type T-cell lymphoma

E. C. Obermann, T. C. Diss, R. A. Hamoudi, B. S. Wilkins, M. L P Camozzi, P. G. Isaacson, M. Q. Du, A. Dogan

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Enteropathy-type T-cell lymphoma (ETL) and ulcerative jejunitis (UJ) are rare disorders often occurring in patients with coeliac disease. The genetic events associated with the accumulation of intraepithelial lymphocytes in coeliac disease and tumour development are largely unknown. Deletions at chromosome 9p21, which harbours the tumour suppressor genes p14/ARF, p15/INK4b, and p16/INK4a, and 17p13, where p53 is located, are associated with the development and progression of lymphomas. To examine whether deletions at 9p21 and 17p13 play a role in ETL, 22 cases of ETL and seven cases of UJ were screened for loss of heterozygosity (LOH) by tissue microdissection and polymerase chain reaction (PCR) analysis for microsatellite markers. Furthermore, p53 and p16 protein expression was examined by immunohistochemistry. In addition, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis for detection of mutations in exons 5-8 of the p53 gene was performed in five cases of ETL and three cases of UJ. LOH was found in at least one microsatellite marker at the 9p21 locus in 8 of 22 (36%) ETLs, but not in UJ. Five of nine (56%) tumours composed of large cells showed LOH at 9p21, as opposed to two of eight (25%) tumours with small- or medium-sized cell morphology. The region spanning the p14/p15/p16 gene locus was most frequently affected (five cases); LOH at these markers coincided with loss of p16 protein expression in all of these cases. p53 overexpression was demonstrated in all ETLs examined and in four of seven cases of UJ. However, no alterations of the p53 gene were detected by LOH or PCR-SSCP analysis. The results of this study show that LOH at chromosome 9p21 is frequent in ETL, especially in tumours with large cell morphology; this finding suggests that gene loss at this locus may play a role in the development of ETL.

Original languageEnglish (US)
Pages (from-to)252-262
Number of pages11
JournalJournal of Pathology
Volume202
Issue number2
DOIs
StatePublished - Feb 2004
Externally publishedYes

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T-Cell Lymphoma
Loss of Heterozygosity
Chromosomes
p53 Genes
Celiac Disease
Microsatellite Repeats
Polymerase Chain Reaction
Neoplasms
Tumor Suppressor Protein p14ARF
p16 Genes
Single-Stranded Conformational Polymorphism
Chromosome Deletion
Microdissection
Tumor Suppressor Genes
Exons
Lymphoma
Proteins
Immunohistochemistry
Lymphocytes
Mutation

Keywords

  • Chromosome 17
  • Chromosome 9
  • Enteropathy-type T-cell lymphoma
  • Loss of heterozygosity
  • p14/ARF
  • p15/INK4b
  • p16/INK4a
  • p53
  • Ulcerative jejunitis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Obermann, E. C., Diss, T. C., Hamoudi, R. A., Wilkins, B. S., Camozzi, M. L. P., Isaacson, P. G., ... Dogan, A. (2004). Loss of heterozygosity at chromosome 9p21 is a frequent finding in enteropathy-type T-cell lymphoma. Journal of Pathology, 202(2), 252-262. https://doi.org/10.1002/path.1506

Loss of heterozygosity at chromosome 9p21 is a frequent finding in enteropathy-type T-cell lymphoma. / Obermann, E. C.; Diss, T. C.; Hamoudi, R. A.; Wilkins, B. S.; Camozzi, M. L P; Isaacson, P. G.; Du, M. Q.; Dogan, A.

In: Journal of Pathology, Vol. 202, No. 2, 02.2004, p. 252-262.

Research output: Contribution to journalArticle

Obermann, EC, Diss, TC, Hamoudi, RA, Wilkins, BS, Camozzi, MLP, Isaacson, PG, Du, MQ & Dogan, A 2004, 'Loss of heterozygosity at chromosome 9p21 is a frequent finding in enteropathy-type T-cell lymphoma', Journal of Pathology, vol. 202, no. 2, pp. 252-262. https://doi.org/10.1002/path.1506
Obermann EC, Diss TC, Hamoudi RA, Wilkins BS, Camozzi MLP, Isaacson PG et al. Loss of heterozygosity at chromosome 9p21 is a frequent finding in enteropathy-type T-cell lymphoma. Journal of Pathology. 2004 Feb;202(2):252-262. https://doi.org/10.1002/path.1506
Obermann, E. C. ; Diss, T. C. ; Hamoudi, R. A. ; Wilkins, B. S. ; Camozzi, M. L P ; Isaacson, P. G. ; Du, M. Q. ; Dogan, A. / Loss of heterozygosity at chromosome 9p21 is a frequent finding in enteropathy-type T-cell lymphoma. In: Journal of Pathology. 2004 ; Vol. 202, No. 2. pp. 252-262.
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abstract = "Enteropathy-type T-cell lymphoma (ETL) and ulcerative jejunitis (UJ) are rare disorders often occurring in patients with coeliac disease. The genetic events associated with the accumulation of intraepithelial lymphocytes in coeliac disease and tumour development are largely unknown. Deletions at chromosome 9p21, which harbours the tumour suppressor genes p14/ARF, p15/INK4b, and p16/INK4a, and 17p13, where p53 is located, are associated with the development and progression of lymphomas. To examine whether deletions at 9p21 and 17p13 play a role in ETL, 22 cases of ETL and seven cases of UJ were screened for loss of heterozygosity (LOH) by tissue microdissection and polymerase chain reaction (PCR) analysis for microsatellite markers. Furthermore, p53 and p16 protein expression was examined by immunohistochemistry. In addition, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis for detection of mutations in exons 5-8 of the p53 gene was performed in five cases of ETL and three cases of UJ. LOH was found in at least one microsatellite marker at the 9p21 locus in 8 of 22 (36{\%}) ETLs, but not in UJ. Five of nine (56{\%}) tumours composed of large cells showed LOH at 9p21, as opposed to two of eight (25{\%}) tumours with small- or medium-sized cell morphology. The region spanning the p14/p15/p16 gene locus was most frequently affected (five cases); LOH at these markers coincided with loss of p16 protein expression in all of these cases. p53 overexpression was demonstrated in all ETLs examined and in four of seven cases of UJ. However, no alterations of the p53 gene were detected by LOH or PCR-SSCP analysis. The results of this study show that LOH at chromosome 9p21 is frequent in ETL, especially in tumours with large cell morphology; this finding suggests that gene loss at this locus may play a role in the development of ETL.",
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AU - Diss, T. C.

AU - Hamoudi, R. A.

AU - Wilkins, B. S.

AU - Camozzi, M. L P

AU - Isaacson, P. G.

AU - Du, M. Q.

AU - Dogan, A.

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N2 - Enteropathy-type T-cell lymphoma (ETL) and ulcerative jejunitis (UJ) are rare disorders often occurring in patients with coeliac disease. The genetic events associated with the accumulation of intraepithelial lymphocytes in coeliac disease and tumour development are largely unknown. Deletions at chromosome 9p21, which harbours the tumour suppressor genes p14/ARF, p15/INK4b, and p16/INK4a, and 17p13, where p53 is located, are associated with the development and progression of lymphomas. To examine whether deletions at 9p21 and 17p13 play a role in ETL, 22 cases of ETL and seven cases of UJ were screened for loss of heterozygosity (LOH) by tissue microdissection and polymerase chain reaction (PCR) analysis for microsatellite markers. Furthermore, p53 and p16 protein expression was examined by immunohistochemistry. In addition, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis for detection of mutations in exons 5-8 of the p53 gene was performed in five cases of ETL and three cases of UJ. LOH was found in at least one microsatellite marker at the 9p21 locus in 8 of 22 (36%) ETLs, but not in UJ. Five of nine (56%) tumours composed of large cells showed LOH at 9p21, as opposed to two of eight (25%) tumours with small- or medium-sized cell morphology. The region spanning the p14/p15/p16 gene locus was most frequently affected (five cases); LOH at these markers coincided with loss of p16 protein expression in all of these cases. p53 overexpression was demonstrated in all ETLs examined and in four of seven cases of UJ. However, no alterations of the p53 gene were detected by LOH or PCR-SSCP analysis. The results of this study show that LOH at chromosome 9p21 is frequent in ETL, especially in tumours with large cell morphology; this finding suggests that gene loss at this locus may play a role in the development of ETL.

AB - Enteropathy-type T-cell lymphoma (ETL) and ulcerative jejunitis (UJ) are rare disorders often occurring in patients with coeliac disease. The genetic events associated with the accumulation of intraepithelial lymphocytes in coeliac disease and tumour development are largely unknown. Deletions at chromosome 9p21, which harbours the tumour suppressor genes p14/ARF, p15/INK4b, and p16/INK4a, and 17p13, where p53 is located, are associated with the development and progression of lymphomas. To examine whether deletions at 9p21 and 17p13 play a role in ETL, 22 cases of ETL and seven cases of UJ were screened for loss of heterozygosity (LOH) by tissue microdissection and polymerase chain reaction (PCR) analysis for microsatellite markers. Furthermore, p53 and p16 protein expression was examined by immunohistochemistry. In addition, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis for detection of mutations in exons 5-8 of the p53 gene was performed in five cases of ETL and three cases of UJ. LOH was found in at least one microsatellite marker at the 9p21 locus in 8 of 22 (36%) ETLs, but not in UJ. Five of nine (56%) tumours composed of large cells showed LOH at 9p21, as opposed to two of eight (25%) tumours with small- or medium-sized cell morphology. The region spanning the p14/p15/p16 gene locus was most frequently affected (five cases); LOH at these markers coincided with loss of p16 protein expression in all of these cases. p53 overexpression was demonstrated in all ETLs examined and in four of seven cases of UJ. However, no alterations of the p53 gene were detected by LOH or PCR-SSCP analysis. The results of this study show that LOH at chromosome 9p21 is frequent in ETL, especially in tumours with large cell morphology; this finding suggests that gene loss at this locus may play a role in the development of ETL.

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KW - Ulcerative jejunitis

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