Variable X‐chromosome DNA methylation patterns detected with probe M27β in a series of lymphoid and myeloid malignancies

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Abstract
In this study the X chromosome probe M27β was used to investigate DNA methylation at the DXS255 locus and hence X inactivation status and determination of tumour clonality in blood, bone marrow and biopsy tissue involved with morphologically and phenotypically defined lymphoid and myeloid disease from 14 female patients along with uninvolved bone marrow from two control individuals. Thirteen out of 16 individuals (81%) were restriction fragment length polymorphism (RFLP) heterozygous for DXSZ 55. DNA methylation status could not be assessed in the three DXS255 homozygous individuals. In eight DXS255 heterozygous individuals clonality was clearly demonstrated using M27β and in six of these cases independent analysis using T cell receptor (TcR) and immunoglobulin (Ig) gene probes confirmed the presence of clonal tumour cell populations. In the two controls, polyclonality was inferred from M27β probe analysis. In the remaining three cases (all acute lymphoblastic leukaemia (ALL)) both DXSZ55 X chromosome sequences appeared to be methylated. Clonality in these cases was demonstrated by TcR or Ig monoclonal gene rearrangements. These data demonstrate the value of the M27β probe for determining tumour clonality in a number of cases with lymphoid and myeloid disease but indicate that there may not always be a complete correlation between DNA methylation, X inactivation status and tumour clonality in certain lymphoid neoplasms, restricting the use of this probe in clonality studies. Correlations between DNA methylation, X inactivation status and stage of normal and neoplastic T and B cell development require further investigation.