Loss of heterozygosity in tumor cells requires re‐evaluation: the data are biased by the size‐dependent differential sensitivity of allele detection

FEBS Letters

Klein, George¹  Zabarovska, Veronika I.¹  Alimov, Andrei¹  Braga, Eleonora¹  Liu, Jian¹  Zabarovsky, Eugene R.¹ 

[1]Microbiology and Tumor Biology Center, Karolinska Institute, Box 280, Stockholm 171 77, Sweden

关键词: Human genetics;    Loss of heterozygosity;    Tumor suppressor gene;    Microsatellite marker;    Human chromosome 3;    Interstitial deletion;    Renal cell carcinoma;    ATA;    allele titration assay;    H allele;    high molecular weight allele;    L allele;    low molecular weight allele;    LOH;    loss of heterozygosity;    MCH;    mouse-human microcell hybrid line;    NPC;    nasopharyngeal carcinoma;    RCC;    renal cell carcinoma;   

DOI  :  10.1016/S0014-5793(99)01523-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Normal tissue contamination of tumors may eclipse the detection of loss of heterozygosity (LOH) by microsatellite analysis and may also hamper isolation of tumor suppressor genes. To test the potential impact of this problem, we prepared artificial mixtures of mouse-human microcell hybrid lines that carried different alleles of the same chromosome 3 marker. After performing an allele titration assay, we found a consistent difference between the LOH of a high molecular weight (H) allele and the LOH of a low molecular weight (L) allele of the same CA repeat marker. It follows that normal tissue admixtures will be less of a problem when LOH affects a H allele than with a L allele. Random screening of 100 papers published between 1994 and 1999 revealed that the loss of a L allele was recorded at about half the frequency (52%) of loss of a H allele. To avoid this bias, we have developed rules for the evaluation of LOH data. We suggest that the loss of a L allele should be given more weight than the loss of a H allele in LOH studies using microsatellite markers.

【 授权许可】

Unknown