SMARCB1/INI1 tumor suppressor gene is frequently inactivated in epithelioid sarcomas
SMARCB1/INI1 tumor suppressor gene is frequently inactivated in epithelioid sarcomas
复制标题
DOI：
10.1158/0008-5472.can-04-3050
复制
发表时间：
2005-05-15
期刊：
影响因子：
11.2
通讯作者：
Sozzi, G
中科院分区：
文献类型：
--
作者：
Modena, P;Lualdi, E;Sozzi, G
上皮样肉瘤是一种罕见的软组织肿瘤，起源不明，通常发生在成年人的四肢远端，复发率和转移率很高，经常造成诊断上的困难。最近报道的大细胞“近端型”变异的特点是侵略性增加，深位置，优先发生在老年患者的近端/轴向区域，横纹肌样特征。先前的细胞遗传学研究表明，与这种肿瘤实体相关的最常见的改变影响22号染色体。在这项研究中，结合光谱核型分析，荧光原位杂交和基于阵列的比较基因组杂交分析的两个近端型的情况下，窝藏涉及10 q26和22 q11重排显示，22 q11断点位于一个150 kb的区域包含SMARCB 1/INI 1基因，该基因的纯合性缺失存在于肿瘤组织。SMARCB 1/INI 1基因编码SWI/SNF染色质重塑复合物的一个不变亚基，以前曾报道在婴儿恶性横纹肌样肿瘤中作为一种经常失活的肿瘤抑制基因。我们分析了SMARCB 1/INI 1基因状态在9个额外的上皮样肉瘤病例（4个近端型和5个传统型），我们总共确定了SMARCB 1/INI 1基因缺失的11例中的5例，所有近端型。我们通过mRNA表达的实时定量PCR分析和SMARCB 1/INI 1免疫组化证实并进一步扩展了SMARCB 1/INI 1失活的病例数至11例中的6例。总之，这些结果表明SMARCB 1/INI 1基因参与上皮样肉瘤的发生和/或进展。需要对更大系列的上皮样肉瘤进行分析，以突出与SMARCB 1/INI 1失活相关的假定临床相关特征。
Epithelioid sarcoma is a rare soft tissue neoplasm of uncertain lineage that usually arises in the distal extremities of adults, presents a high rate of recurrences and metastases and frequently poses diagnostic dilemmas. The recently reported large-cell "proximal-type" variant is characterized by increased aggressiveness, deep location, preferential occurrence in proximal/axial regions of older patients, and rhabdoid features. Previous cytogenetic studies indicated that the most frequent alterations associated with this tumor entity affect chromosome 22. In this study, combined spectral karyotyping, fluorescence in situ hybridization, and array-based comparative genomic hybridization analyses of two proximal-type cases harboring a rearrangement involving 10q26 and 22q11 revealed that the 22q11 breakpoints were located in a 150-kb region containing the SMARCB1/INI1 gene, and that homozygous deletion of the gene was present in the tumor tissue. The SMARCB1/INI1 gene encodes for an invariant subunit of SWI/SNF chromatin remodeling complex and has been previously reported to act as a tumor suppressor gene frequently inactivated in infantile malignant rhabdoid tumors. We analyzed SMARCB1/INI1 gene status in nine additional epithelioid sarcoma cases (four proximal types and five conventional types) and altogether we identified deletions of SMARCB1/INI1 gene in 5 of 11 cases, all proximal types. We confirmed and further extended the number of cases with SMARCB1/INI1 inactivation to 6 of 11 cases, by real-time quantitative PCR analysis of mRNA expression and by SMARCB1/INI1 immunohistochemistry. Overall, these results point to SMARCB1/INI1 gene involvement in the genesis and/or progression of epithelioid sarcomas. Analysis of larger series of epithelioid sarcomas will be necessary to highlight putative clinically relevant features related to SMARCB1/INI1 inactivation.