Sahlin P, Mark J, Stenman G
Department of Pathology, University of Göteborg, Sahlgren's Hospital, Sweden.
Genes Chromosomes Cancer. 1994 Aug;10(4):256-61. doi: 10.1002/gcc.2870100406.
A subgroup of benign pleomorphic adenomas of the salivary glands is characterized by translocations, or on rare occasions deletions, with breakpoints at 3p21. We have applied restriction fragment length polymorphism (RFLP) analysis to assess the frequency of allelic losses at four different loci located within 3p21-->p25 in 35 pleomorphic adenomas, 18 of which were also karyotyped. Parallel analysis of constitutional and tumor DNAs in informative tumors revealed that all patients retained heterozygosity in their tumor DNA at the D3S2 and RAF1 loci. Among the 29 tumors informative for THRB three showed loss of heterozygosity (LOH). All three tumors had a t(3;8)(p21;q12). Of the 23 tumors informative for D3F15S2, one showed LOH. This tumor also had a t(3;8)(p21;q12). To further map the deletions in relation to the 3p21 translocation breakpoint, we also sublocalized the THRB locus. Using in situ hybridization we assigned the gene to 3p24.1-3. The fact that none of the tumors with loss of 3p alleles showed cytogenetic evidence of deletions indicates that the losses are submicroscopic, probably interstitial, and in most cases distal to the 3p21 breakpoint. This was confirmed in one case with loss of a THRB allele where both proximal (D3F15S2) and distal (RAF1) markers retained heterozygosity. Our results suggest that deletion of 3p sequences might be of progressional importance in a subset of pleomorphic adenomas with t(3;8)(p21;q12).
涎腺良性多形性腺瘤的一个亚组的特征是存在易位，或在极少数情况下存在缺失，断点位于3p21。我们应用限制性片段长度多态性（RFLP）分析，以评估35例多形性腺瘤中位于3p21→p25区域内4个不同位点的等位基因缺失频率，其中18例还进行了核型分析。对信息丰富的肿瘤中的正常和肿瘤DNA进行平行分析发现，所有患者的肿瘤DNA在D3S2和RAF1位点均保持杂合性。在29例对THRB信息丰富的肿瘤中，3例显示杂合性缺失（LOH）。所有这3例肿瘤均有t(3;8)(p21;q12)。在23例对D3F15S2信息丰富的肿瘤中，1例显示LOH。该肿瘤也有t(3;8)(p21;q12)。为了进一步确定与3p21易位断点相关的缺失区域，我们还对THRB位点进行了亚定位。通过原位杂交，我们将该基因定位于3p24.1 - 3。3p等位基因缺失的肿瘤均未显示出缺失的细胞遗传学证据，这一事实表明这些缺失是亚显微的，可能是间质性的，并且在大多数情况下位于3p21断点的远端。在1例THRB等位基因缺失的病例中得到证实，其中近端（D3F15S2）和远端（RAF1）标记均保持杂合性。我们的结果表明，3p序列的缺失可能在一部分具有t(3;8)(p21;q12)的多形性腺瘤的进展中具有重要意义。
