Frequent homozygous deletions of the D13S25 locus in chromosome region 13q14 defines the location of a gene critical in leukaemogenesis in chronic B-cell lymphocytic leukaemia

R. M. Chapman, M. M. Corcoran, A. Gardiner, Lesleyann Hawthorn, John Kenneth Cowell, D. G. Oscier

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Abstract

Cytogenetic studies of B-cell chronic lymphocytic leukaemia show structural abnormalities involving the 13q14 chromosome region as the only karyotypic change in a significant proportion of tumours. This observation suggests the location of a gene important in leukaemogenesis. A series of 68 BCLL tumours have been analysed for allele loss using a series of probes from 13q14. Using intragenic polymorphic markers from the retinoblastoma predisposition gene LOH was observed in 25% of tumours including 3/6 showing cytogenetically obvious deletions of the 13q14 region and 3/6 showing translocations involving 13q14. However, three deletions with proximal breakpoints in 13q14 did not show allele loss, demonstrating that the breakpoint lay distal to RB1. Using the D13S25 locus, which lies 1.6 cM distal to RB1, allele loss was seen in 90% of tumours with structural rearrangements of 13q14 and 75% of tumours with an apparently normal karyotype. 50% of these tumours showed homozygous loss of D13S25, suggesting that a 'tumour suppressor gene' lies in this region. The more distal D13S31 locus, 1 cM distal to D13S25, was infrequently involved in allele loss demonstrating that the minimum region of overlap for homozygous deletions is approximately 1 Mhp around the D13S25 locus.

Original languageEnglish (US)
Pages (from-to)1289-1293
Number of pages5
JournalOncogene
Volume9
Issue number4
StatePublished - Apr 1 1994
Externally publishedYes

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B-Cell Chronic Lymphocytic Leukemia
Chromosomes
Alleles
Genes
Neoplasms
Retinoblastoma Genes
Tumor Suppressor Genes
Karyotype
Cytogenetics

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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Frequent homozygous deletions of the D13S25 locus in chromosome region 13q14 defines the location of a gene critical in leukaemogenesis in chronic B-cell lymphocytic leukaemia. / Chapman, R. M.; Corcoran, M. M.; Gardiner, A.; Hawthorn, Lesleyann; Cowell, John Kenneth; Oscier, D. G.

In: Oncogene, Vol. 9, No. 4, 01.04.1994, p. 1289-1293.

Research output: Contribution to journalArticle

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abstract = "Cytogenetic studies of B-cell chronic lymphocytic leukaemia show structural abnormalities involving the 13q14 chromosome region as the only karyotypic change in a significant proportion of tumours. This observation suggests the location of a gene important in leukaemogenesis. A series of 68 BCLL tumours have been analysed for allele loss using a series of probes from 13q14. Using intragenic polymorphic markers from the retinoblastoma predisposition gene LOH was observed in 25{\%} of tumours including 3/6 showing cytogenetically obvious deletions of the 13q14 region and 3/6 showing translocations involving 13q14. However, three deletions with proximal breakpoints in 13q14 did not show allele loss, demonstrating that the breakpoint lay distal to RB1. Using the D13S25 locus, which lies 1.6 cM distal to RB1, allele loss was seen in 90{\%} of tumours with structural rearrangements of 13q14 and 75{\%} of tumours with an apparently normal karyotype. 50{\%} of these tumours showed homozygous loss of D13S25, suggesting that a 'tumour suppressor gene' lies in this region. The more distal D13S31 locus, 1 cM distal to D13S25, was infrequently involved in allele loss demonstrating that the minimum region of overlap for homozygous deletions is approximately 1 Mhp around the D13S25 locus.",
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