PLAG1 alterations in lipoblastoma -: Involvement in varied mesenchymal cell types and evidence for alternative oncogenic mechanisms
PLAG1 alterations in lipoblastoma -: Involvement in varied mesenchymal cell types and evidence for alternative oncogenic mechanisms
复制标题
DOI：
10.1016/s0002-9440(10)61771-3
复制
发表时间：
2001-09-01
影响因子：
6
通讯作者：
Fletcher, JA
中科院分区：
文献类型：
--
作者：
Gisselsson, D;Hibbard, MK;Fletcher, JA
脂肪母细胞瘤是一种罕见的软组织肿瘤，主要发生在幼儿。它们通常含有未分化的脂肪细胞、原始间充质细胞、粘液样基质和纤维小梁。最近在4例脂肪母细胞瘤中证实了8号染色体的缺失，导致PLAG1基因重排。在本报告中，我们确定了16例13岁或以下儿童脂肪母细胞瘤中PLAG1基因改变的频率，我们还评估了脂肪母细胞瘤分化的阶段，其中PLAG1基因组改变被发现。11例脂肪母细胞瘤（69%），包括那些经典或脂肪瘤样组织学，有8q12 PLAG1区域重排。另外3例脂肪母细胞瘤为8号染色体多体性，PLAG1重排缺失。只有2例（13%）缺乏8号染色体异常。值得注意的是，具有8号染色体多体性的脂肪母细胞瘤具有多达5个8号染色体拷贝，作为在其他二倍体细胞中的孤立的细胞遗传学发现。我们还证明，PLAG1的改变被发现在脂肪母细胞瘤，包括脂肪母细胞，成熟脂肪细胞，原始间充质细胞，成纤维细胞样细胞的间充质细胞类型的频谱。这一发现与肿瘤起源于原始间充质前体和分化为成熟脂肪细胞终点的可变性一致。因此，我们的研究提供了生物学验证的临床观察，脂肪母细胞瘤可以演变成成熟的，脂肪瘤样，病变。他们还表明，由多体性8引起的PLAG1剂量改变可能代表脂肪母细胞瘤中的另一种致癌机制。
Lipoblastomas are rare soft tissue tumors that occur primarily in young children. They typically contain variably differentiated adipocytes, primitive mesenchymal cells, myxoid matrix, and fibrous trabeculae. Abnormalities in chromosome 8, leading to rearrangements of the PLAG1 gene, were demonstrated recently in four lipoblastomas. In the present report, we determine the frequency of PLAG1 alterations in 16 lipoblastomas from children aged 13 years or younger, and we also evaluate the stages of lipoblastoma differentiation at which PLAG1 genomic alterations are found. Eleven lipoblastomas (69%), including those with either classic or lipoma-like histology, had rearrangements of the 8q12 PLAG1 region. Another three lipoblastomas had polysomy for chromosome 8 In the absence of PLAG1 rearrangement. Only two cases (13%) lacked a chromosome 8 abnormality. Notably, the lipoblastomas with chromosome 8 polysomy had up to five copies of chromosome 8 as an isolated cytogenetic finding in an otherwise diploid cell. We also demonstrate that PLAG1 alterations are found in a spectrum of mesenchymal cell types in lipoblastomas, including lipoblasts, mature adipocytes, primitive mesenchymal cells, and fibroblastlike cells. This finding is consistent with neoplastic origin in a primitive mesenchymal precursor and with variable differentiation to a mature adipocyte end-point. Hence, our studies provide biological validation for the clinical observation that lipoblastomas can evolve into mature, lipoma-like, lesions. They also suggest that PLAG1 dosage alterations caused by polysomy 8 might represent an alternative oncogenic mechanism in lipoblastoma.