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. 2002 Oct;161(4):1507-13.
doi: 10.1016/S0002-9440(10)64426-4.

Chromosome 6 suffers frequent and multiple aberrations in thymoma

Masayoshi Inoue  1 , Alexander Marx, Andreas Zettl, Philipp Ströbel, Hans-Konrad Müller-Hermelink, Petr Starostik
Affiliations

Chromosome 6 suffers frequent and multiple aberrations in thymoma

Masayoshi Inoue et al. Am J Pathol. 2002 Oct.

Abstract

Thymoma is the most frequent tumor arising in human thymus. In this study, we performed a detailed mapping of deleted regions on chromosome 6 shown previously to harbor the most frequent genetic aberrations in this cancer. We analyzed 40 thymomas using 41 microsatellites. Two hundred ninety-four (23.5%) of 1253 informative genotypes showed loss of heterozygosity (LOH), only 39 (2.4%) were positive for microsatellite instability (MSI). Genetic aberrations on chromosome 6 were found in 31 of 40 cases (77.5%) in five hot spots. The most frequent LOHs (48.6%) occurred in region 6q25.2 within a 0.7-Mb interval flanked by markers D6S441 and D6S290. Another hot spot showing LOH in 32.4% of tumors was located between markers D6S442 and D6S1708 (0.4 Mb apart) on 6q25.2-25.3, just 1.1 Mb from the D6S441-D6S290 deletions. The third hot spot (30%) showing LOH appeared in region 6p21.31 including the MHC locus (markers D6S1666-D6S1560, 1 Mb apart). The fourth hot spot (26.3%) was detected on 6q14.1-14.3 (D6S1596-D6S284, 5.2 Mb apart). Some tumors (21.6%) showed LOHs within a fifth hot spot on 6q21 (D6S447-D6S1592, 0.3 Mb apart). Thus, several tumor suppressor genes on chromosome 6 seem to be involved in the pathogenesis of thymoma.

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Figures

Figure 1.
Figure 1.
Example of microsatellite analysis and CGH results. A: LOH. Control and tumor DNAs of case no. 14 were amplified with marker D6S473. The first allele signal intensity (180 bp, arrow) decreased by 90% as compared to the control. B: Corresponding partial loss of 6q24-qter detected by CGH.
Figure 2.
Figure 2.
A: 6q25.2 and 6q25.2-25.3 LOH hot spots as defined by markers D6S441-D6S290 and D6S442-D6S1708, respectively. Status of each locus and its position (according to the Ensembl database) is indicated: filled boxes, LOH; vertically striped boxes, MSI; boxes with right hexagonal lines, retention of heterozygosity; open boxes, homozygosity; NA, no amplificate. B: 6p21.31 LOH hot spot as defined by markers D6S1666 and D6S1560. C: 6q14.1-14.3 LOH hot spot as defined by markers D6S1596 and D6S284. D: 6q21 LOH hot spot as defined by markers D6S447 and D6S1592.
Figure 3.
Figure 3.
Example of MSI. Control and tumor DNAs of case no. 28 were amplified with marker D6S1708. Tumor DNA shows a new additional allele (160 bp, arrow).
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