Original Article
Subject Category: Tumor Biology
Journal of Investigative Dermatology (2006) 126, 1893–1899. doi:10.1038/sj.jid.5700304; published online 1 June 2006
Molecular Analysis of T-Cell Receptor
Genes in Cutaneous T-Cell Lymphoma Reveals J
1 Bias
Suzanne M Morgan1, Elizabeth Hodges1, Tracey J Mitchell2, Susan Harris1, Sean J Whittaker2 and John L Smith1
- 1Molecular Pathology, Cancer Sciences Division, School of Medicine, General Hospital, Southampton University Hospitals NHS Trust, Southampton, UK
- 2Skin Tumour Unit, St John's Institute of Dermatology, St Thomas' Hospital, London, UK
Correspondence: Dr Elizabeth Hodges, Molecular Pathology, Cancer Sciences Division, General Hospital, Southampton University Hospitals NHS Trust, Southampton SO16 6YD, UK. E-mail: elizabeth.hodges@suht.swest.nhs.uk
Received 27 September 2005; Revised 25 November 2005; Accepted 1 February 2006; Published online 1 June 2006.
Abstract
Molecular characterization of T-cell receptor junctional region sequences in cutaneous T-cell lymphoma had not been previously reported. We have examined in detail the features of the T-cell receptor beta (TCRB) gene rearrangements in 20 individuals with well-defined stages of cutaneous T-cell lymphoma (CTCL) comprising 10 cases with early-stage mycosis fungoides (MF) and 10 cases with late-stage MF or Sezary syndrome. Using BIOMED-2 PCR primers, we detected a high frequency of clonally rearranged TCR gamma and TCRB genes (17/20 and 15/20 cases, respectively). We carried out sequencing analysis of each complete clonal variable (V)
–diversity (D)
–joining(J)
fingerprint generated by PCR amplification, and determined the primary structure of the V
–D
–J
junctional regions. We observed considerable diversity in the T-cell receptor V
gene usage and complementarity-determining region 3 loops. Although we found that TCRB gene usage in CTCL and normal individuals share common features, our analysis also revealed preferential usage of J
1 genes in all cases with advanced stages of disease.
Abbreviations:
CDR3, complementarity-determining region 3; CTCL, cutaneous T-cell lymphoma; D, diversity; J, joining; MF, mycosis fungoides; SS, Sezary syndrome; TCR, T-cell receptor; TCRB, TCR beta; TCRG, TCR gamma; V, variable
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