Genetic profiling of a chondroblastoma-like osteosarcoma/malignant phosphaturic mesenchymal tumor of bone reveals a homozygous deletion of CDKN2A, intragenic deletion of DMD, and a targetable FN1-FGFR1 gene fusion
Genetic profiling of a chondroblastoma-like osteosarcoma/malignant phosphaturic mesenchymal tumor of bone reveals a homozygous deletion of CDKN2A, intragenic deletion of DMD, and a targetable FN1-FGFR1 gene fusion
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DOI：
10.1002/gcc.22764
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发表时间：
2019-10-01
影响因子：
3.7
通讯作者：
Nord, Karolin H.
中科院分区：
文献类型：
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作者：
Saba, Karim H.;Cornmark, Louise;Nord, Karolin H.
传统骨肉瘤是最常见的原发性骨恶性肿瘤。这组肿瘤根据具体的组织学特征进行亚分类，但迄今为止亚型、治疗和预后之间没有相关性。通过对软骨母细胞瘤样骨肉瘤的深入遗传分析，我们发现了一种与以前报道的良性和恶性骨肿瘤不同的遗传特征。总体基因组拷贝数谱比通常与传统骨肉瘤相关的基因组拷贝数谱不那么复杂，并且在H3 F3 A、H3 F3 B、IDH 1、IDH 2、BRAF或GNAS中没有激活点突变。相反，我们发现了一个纯合的CDKN 2A缺失，DMD微缺失和FN 1-FGFR 1基因融合。后一种改变在磷酸尿性间叶细胞瘤中有描述。这种肿瘤类型与软骨母细胞瘤样骨肉瘤有一些共同的形态学特征，我们不能排除本例实际上代表了一种FN 1-FGFR 1阳性的恶性磷酸盐尿性骨间质肿瘤，但没有骨软化。
Conventional osteosarcoma is the most common primary malignancy of bone. This group of neoplasms is subclassified according to specific histological features, but hitherto there has been no correlation between subtype, treatment, and prognosis. By in-depth genetic analyses of a chondroblastoma-like osteosarcoma, we detect a genetic profile that is distinct from those previously reported in benign and malignant bone tumors. The overall genomic copy number profile was less complex than that typically associated with conventional osteosarcoma, and there was no activating point mutation in any of H3F3A, H3F3B, IDH1, IDH2, BRAF, or GNAS. Instead, we found a homozygous CDKN2A deletion, a DMD microdeletion and an FN1-FGFR1 gene fusion. The latter alteration has been described in phosphaturic mesenchymal tumor. This tumor type shares some morphological features with chondroblastoma-like osteosarcoma and we cannot rule out that the present case actually represents an FN1-FGFR1 positive malignant phosphaturic mesenchymal tumor of bone without osteomalacia.