Nucci M R, Weremowicz S, Neskey D M, Sornberger K, Tallini G, Morton C C, Quade B J
Division of Women's and Perinatal Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Genes Chromosomes Cancer. 2001 Oct;32(2):172-6. doi: 10.1002/gcc.1179.
Benign mesenchymal neoplasms associated with rearrangements of the DNA architectural factor gene HMGIC on chromosome 12 include lipomas, uterine leiomyomata, pulmonary chondroid hamartomas, endometrial polyps, salivary gland pleomorphic adenomas, and breast fibroadenomas. Although HMGIC also has been implicated in the pathobiology of aggressive angiomyxoma of the vulva, the molecular mechanisms pertaining to this neoplasm are unclear. Tissue from a recurrent aggressive angiomyxoma was investigated by cytogenetic and expression analysis for HMGIC and HMGIY. The trypsin-Giemsa-banded karyotype showed a clonal translocation between chromosomes 8 and 12 [46,XX,t(8;12)(p12;q15)]. Fluorescence in situ hybridization (FISH) analysis with whole chromosome paint probes for chromosomes 8 and 12 excluded cryptic involvement of other chromosomes. The chromosome 12 breakpoint was mapped with two-color FISH analysis using cosmid probes at the 5' and 3' termini of HMGIC. Both cosmid probes showed hybridization to the normal chromosome 12 and the der(12) chromosome, indicating that the breakpoint was 3' (telomeric) to the gene. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed HMGIC expression in the tumor, and immunohistochemistry localized HMGIC expression to the tumor's spindle cells. Like numerous benign mesenchymal tumors, this locally aggressive tumor is associated with rearrangements near or within HMGIC, but chimeric gene formation was not required for tumorigenesis. Inappropriate expression of this DNA binding protein, however, may be important in the pathobiology of this tumor. Understanding the pathogenetic mechanism may also be helpful in developing new diagnostic tools for identifying residual disease.
与12号染色体上DNA结构因子基因HMGIC重排相关的良性间叶肿瘤包括脂肪瘤、子宫平滑肌瘤、肺软骨样错构瘤、子宫内膜息肉、涎腺多形性腺瘤和乳腺纤维腺瘤。虽然HMGIC也与外阴侵袭性血管黏液瘤的病理生物学有关，但该肿瘤的分子机制尚不清楚。通过细胞遗传学和HMGIC及HMGIY的表达分析，对一例复发性侵袭性血管黏液瘤的组织进行了研究。胰蛋白酶-吉姆萨显带核型显示8号和12号染色体之间存在克隆性易位[46,XX,t(8;12)(p12;q15)]。用8号和12号染色体的全染色体涂染探针进行荧光原位杂交（FISH）分析，排除了其他染色体的隐匿性参与。使用位于HMGIC 5'和3'末端的黏粒探针，通过双色FISH分析对12号染色体的断点进行了定位。两个黏粒探针均显示与正常12号染色体和der(12)染色体杂交，表明断点位于该基因的3'（端粒）侧。逆转录聚合酶链反应（RT-PCR）分析显示肿瘤中有HMGIC表达，免疫组化将HMGIC表达定位于肿瘤的梭形细胞。与许多良性间叶肿瘤一样，这种局部侵袭性肿瘤与HMGIC附近或内部的重排有关，但肿瘤发生并不需要嵌合基因的形成。然而，这种DNA结合蛋白的不适当表达可能在该肿瘤的病理生物学中起重要作用。了解发病机制可能也有助于开发用于识别残留疾病的新诊断工具。
