Journal Article

Allelic imbalance at intragenic markers of <i>Tbx18</i> is a hallmark of murine osteosarcoma

M. Rosemann, V. Kuosaite, M. Nathrath, T.M. Strom, L. Quintanilla-Martinez, T. Richter, K. Imai and M.J. Atkinson

in Carcinogenesis

Volume 24, issue 3, pages 371-376
Published in print March 2003 | ISSN: 0143-3334
Published online March 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/24.3.371
Allelic imbalance at intragenic markers of Tbx18 is a hallmark of murine osteosarcoma

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We have recently identified a locus exhibiting a high frequency of allelic imbalance (AI) in both spontaneous human (HSA 6q14.1-15) and radiogenic murine (MMU9, 42 cM) osteosarcoma. Here we describe the fine mapping of the locus in osteosarcoma arising in (BALB/c×CBA) F1 hybrid mice. These studies have allowed us to identify Tbx18, a member of the T-box transcriptional regulator gene family, as a candidate gene. Three intragenic Tbx18 polymorphisms were used to map the region of maximum AI to within the gene itself; 16 of 17 tumours exhibited imbalances of at least one of these markers. The highest frequency was found in exon 1, where 14 of 17 tumours were affected at a single nucleotide polymorphism at 541 nt. Two polymorphic CA repeat markers in intron 2 and intron 5 demonstrated overlapping regions of imbalance in several tumours. Both markers flanking the Tbx18 gene (D9Osm48 and D9Mit269) revealed significantly lower frequencies of imbalance and confirmed the limitation of the common interval to Tbx18. Examination of both the mouse and human annotated genomic sequences indicated Tbx18 to be the only gene within the interval. Sequence analysis of the Tbx18 coding region did not reveal any evidence of mutation. Given the haploinsufficiency phenotypes reported for other T-box genes, we speculate that AI may influence the function of Tbx18 during osteosarcomagenesis.

Keywords: AI, allelic imbalance; PCR, polymerase chain reaction.

Journal Article.  4711 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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