CLONAL ANALYSIS OF HUMAN TUMORS WITH M27-BETA, A HIGHLY INFORMATIVE POLYMORPHIC-X CHROMOSOMAL PROBE

被引:105
作者
FEY, MF
PETER, HJ
HINDS, HL
ZIMMERMANN, A
LIECHTIGALLATI, S
GERBER, H
STUDER, H
TOBLER, A
机构
[1] TIEFENAU HOSP BERN,CLIN & EXPTL RES LAB,BERN,SWITZERLAND
[2] INSELSPITAL BERN,DEPT MED,CH-3010 BERN,SWITZERLAND
[3] UNIV OXFORD,DEPT BIOCHEM,GENET LAB,OXFORD,ENGLAND
[4] UNIV BERN,DEPT PATHOL,CH-3000 BERN,SWITZERLAND
[5] INSELSPITAL BERN,DEPT PAEDIAT,DIV GENET,CH-3010 BERN,SWITZERLAND
[6] INSELSPITAL BERN,CENT HAEMATOL LAB,CH-3010 BERN,SWITZERLAND
关键词
X-CHROMOSOME METHYLATION; X-LINKED VNTR; TUMOR CLONALITY; THYROID NODULES; X-INACTIVATION SKEWING;
D O I
10.1172/JCI115733
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The clonality of human tumors can be studied by X inactivation/methylation analysis in female patients heterozygous for X-linked DNA polymorphisms. We present a detailed study on clonal tumor analysis with M27-beta, a highly informative probe detecting a polymorphic X chromosomal locus, DXS255. The polymorphism detected at this locus is due to variable numbers of tandem repeats. The rate of constitutional heterozygosity detected by M27-beta was 88%. Normal tissue from gastrointestinal mucosa and thyroid showed random, hence polyclonal, patterns. Nonrandom clonal X inactivation was detected in all 22 malignant neoplasms that had been shown to be clonal by other DNA markers, such as antigen receptor gene rearrangements or clonal loss of heterozygosity at 17p and other loci. 16/48 normal blood leukocyte samples (33%) showed considerably skewed X inactivation patterns. Comparison of blood leukocytes and normal tissue indicated that in a given individual, X inactivation patterns may be tissue specific. M27-beta was used to study the clonal composition of 13 benign thyroid nodules from 12 multinodular goiters with rapid recent growth, traditionally termed "adenomas." Nine of them were clonal, whereas four nodules and tissue from a case of Graves'goiter were not, indicating that some, but not all, such thyroid nodules may represent true clonal neoplasms. The M27-beta probe permits one to study the clonal composition by the X inactivation approach of a wide variety of solid tumors from most female patients. As a control, normal tissue homologous to the tumor type of interest is preferable to DNA from blood leukocytes, since the latter may show nonrandom X inactivation patterns in a fairly high proportion of cases. M27-beta may, therefore, be of limited use for the clonal analysis of neoplasms derived from hematopoietic cells.
引用
收藏
页码:1438 / 1444
页数:7
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