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 bold italic beta Genes in Cutaneous T-Cell Lymphoma Reveals Jbold italic beta1 Bias

Suzanne M Morgan1, Elizabeth Hodges1, Tracey J Mitchell2, Susan Harris1, Sean J Whittaker2 and John L Smith1

  1. 1Molecular Pathology, Cancer Sciences Division, School of Medicine, General Hospital, Southampton University Hospitals NHS Trust, Southampton, UK
  2. 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.

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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)beta–diversity (D)beta–joining(J)beta fingerprint generated by PCR amplification, and determined the primary structure of the VbetaDbetaJbeta junctional regions. We observed considerable diversity in the T-cell receptor Vbeta 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 Jbeta1 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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