Common somatic alterations identified in maffucci syndrome by molecular karyotyping.
Common somatic alterations identified in maffucci syndrome by molecular karyotyping.
复制标题
通过分子核型分析发现马夫奇综合征中常见的体细胞改变。
DOI：
10.1159/000365898
复制
发表时间：
2014
影响因子：
1.1
通讯作者：
Vikkula,Miikka
中科院分区：
文献类型：
--
作者：
Amyere,Mustapha;Dompmartin,Anne;Wouters,Vinciane;Enjolras,Odile;Kaitila,Ilkka;Docquier,Pierre-Louis;Godfraind,Catherine;Mulliken,JohnButler;Boon,LaurenceMyriam;Vikkula,Miikka
马夫奇综合征（MS）是一种罕见的先天性疾病，其特征是多发性中央软骨瘤（内软骨瘤）与皮肤梭形细胞血管瘤有关。这些患者恶性转化的发生率高。没有家族性病例，致病原因尚不清楚。在仅由内软骨瘤组成的内软骨瘤病（olliver disease， OD）中，在4例患者中发现了PTHR1基因的4个突变；体细胞细胞3只，种系细胞1只。MS患者中未检测到PTHR1突变，而在77%的MS患者和81%的OD患者中观察到体细胞IDH1和更罕见的IDH2突变。这些基因改变与其他肿瘤一样，包括神经胶质瘤、白血病和癌症。为了寻找潜在的体细胞基因组原因，我们使用Affymetrix snp芯片筛选MS组织。我们通过对肿瘤DNA和相应的血液提取DNA中的等位基因强度进行两两分析，寻找CNVs、LOH和单系异位体（UPID）。虽然在体质DNA中没有常见的染色体异常，但在ms相关肿瘤中发现了几个共享的CNVs。最常见的体细胞改变定位于2p22。3、2抓起。3和14q11。在一个软骨肉瘤标本中，在3、6、9、10、12、13和19号染色体上观察到大量扩增和/或缺失。在其他软骨肉瘤中也报道了这些基因变化，提示其具有致病作用。Maffucci组织未见LOH/UPID。我们的发现确定了2p22上频繁的体细胞染色体重排。3、2抓起。3和14q11。2，这可能会揭示导致MS病理特征病变的突变。
Maffucci syndrome (MS) is a rare congenital disorder characterized by multiple central cartilaginous tumors (enchondromas) in association with cutaneous spindle cell hemangiomas. These patients have a high incidence of malignant transformation. No familial case is known and the etiopathogenic cause remains unknown. In enchondromatosis (Ollier disease, OD), which is comprised of enchondromas only, 4 mutations in the PTHR1 gene have been identified in 4 patients; 3 were somatic and 1 was germline. No PTHR1 mutations have been detected in MS, whereas somatic IDH1 and, more rarely, IDH2 mutations have been observed in 77% of patients with MS and 81% of patients with OD. These genetic alterations are shared with other tumors, including glioma, leukemia and carcinoma. To search for underlying somatic genomic causes, we screened MS tissues using Affymetrix SNP-chips. We looked for CNVs, LOH and uniparental isodisomy (UPID) by performing pairwise analyses between allelic intensities in tumoral DNA versus the corresponding blood-extracted DNA. While common chromosomal anomalies were absent in constitutional DNA, several shared CNVs were identified in MS-associated tumors. The most frequently encountered somatic alterations were localized in 2p22. 3, 2q24. 3 and 14q11. 2, implicating these chromosomal rearrangements in the formation of enchondromas and spindle cell hemangiomas in MS. In one chondrosarcoma specimen, large amplifications and/or deletions were observed in chromosomes 3, 6, 9, 10, 12, 13, and 19. Some of these genetic changes have been reported in other chondrosarcomas suggesting an etiopathogenic role. No LOH/UPID was observed in any Maffucci tissue. Our findings identify frequent somatic chromosomal rearrangements on 2p22. 3, 2q24. 3 and 14q11. 2, which may unmask mutations leading to the lesions pathognomonic of MS.