Chromosome 3p loss of heterozygosity and reduced expression of H3K36me3 correlate with longer relapse-free survival in sacral conventional chordoma.
Chromosome 3p loss of heterozygosity and reduced expression of H3K36me3 correlate with longer relapse-free survival in sacral conventional chordoma.
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DOI：
10.1016/j.humpath.2020.07.002
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发表时间：
2020-10
期刊：
影响因子：
3.3
通讯作者：
Hameed MR
中科院分区：
文献类型：
--
作者：
Zhu GG;Ramirez D;Chen W;Lu C;Wang L;Frosina D;Jungbluth A;Ntiamoah P;Nafa K;Boland PJ;Hameed MR
传统脊索瘤是一种罕见的缓慢生长的脊索来源的恶性肿瘤，主要发生在颅底和骶尾骨。脊索瘤可能源自其良性对应物良性脊索细胞肿瘤，并且也可以经历去分化进展为去分化脊索瘤。尚无研究直接比较这些肿瘤之间构成形态连续体的基因组改变。我们之前的研究发现，3p 染色体经常发生杂合性丢失，并且 3 号染色体上包含 SETD2 的缺失区域最少，SETD2 编码参与组蛋白 H3 赖氨酸 36 (H3K36me3) 三甲基化的组蛋白甲基转移酶。在当前的研究中，我们使用 SNP 阵列、靶向下一代测序分析和免疫组织化学将研究范围扩大到包括 65 例骶骨传统脊索瘤病例、3 例良性脊索细胞肿瘤和 2 例去分化脊索瘤。我们对组蛋白 H3K36me3 进行了免疫组织化学分析，并研究了临床行为与复发染色体或非整倍体或 H3K36me3 蛋白表达之间是否存在任何关联。我们发现，从良性脊索细胞肿瘤到传统脊索瘤，再到去分化脊索瘤，基因组不稳定性增加。高度复发的基因组畸变，即染色体 3p 杂合性缺失（发生在 70% 的传统脊索瘤中），与较长的无复发生存期相关，但与骶骨脊索瘤的总生存期或无转移生存期无关。脊索瘤表现出 H3K36me3 表达的不同模式和水平，并且 H3K36me3 表达的减少与较长的无复发生存期有轻微的显着相关性。编码 H3K36me3 甲基化转移酶复合物和去甲基化酶的基因的拷贝数改变可能是 H3K36me3 表达水平改变的原因。
Conventional chordoma is a rare slow-growing malignant tumor of notochordal origin primarily arising at base of skull and sacrococcygeal bones. Chordoma may arise from its benign counterpart, benign notochordal cell tumors, and can also undergo dedifferentiation progressing into dedifferentiated chordoma. No study has directly compared the genomic alterations among these tumors comprising a morphologic continuum. Our prior study identified frequent chromosome 3p loss of heterozygosity and minimum deleted regions on chromosome 3 encompassing SETD2, encoding a histone methyltransferase involved in the trimethylation of lysine-36 of histone H3 (H3K36me3). In the current study we expanded our study to include 65 sacral conventional chordoma cases, 3 benign notochordal cell tumors and 2 dedifferentiated chordomas using SNP array, targeted Next-Generation Sequencing analysis and immunohistochemistry. We performed immunohistochemical analysis of histone, H3K36me3 and investigated whether there is any association between the clinical behavior and recurrent chromosome or aneuploidy, or H3K36me3 protein expression. We found that there is increased genomic instability from benign notochordal cell tumor to conventional chordoma, to dedifferentiated chordoma. The highly recurrent genomic aberration, chromosome 3p loss of heterozygosity (occurred in 70% of conventional chordomas), is correlated with longer relapse free survival, but not with overall survival or metastasis free survival in sacral chordoma. Chordomas demonstrate variable patterns and levels of H3K36me3 expression and reduced expression of H3K36me3 showed marginally significant correlation with longer relapse free survival. Copy number alterations in the genes encoding H3K36me3 methylation transferase complex and demethylase may account for the altered H3K36me3 expression levels.
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影响因子：
7.7
作者：
Hieronymus H;Murali R;Tin A;Yadav K;Abida W;Moller H;Berney D;Scher H;Carver B;Scardino P;Schultz N;Taylor B;Vickers A;Cuzick J;Sawyers CL
通讯作者：
Sawyers CL
DOI：
10.1158/1078-0432.ccr-12-3886
发表时间：
2013-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hakimi AA;Ostrovnaya I;Reva B;Schultz N;Chen YB;Gonen M;Liu H;Takeda S;Voss MH;Tickoo SK;Reuter VE;Russo P;Cheng EH;Sander C;Motzer RJ;Hsieh JJ;ccRCC Cancer Genome Atlas (KIRC TCGA) Research Network investigators
通讯作者：
ccRCC Cancer Genome Atlas (KIRC TCGA) Research Network investigators
影响因子：
5.6
作者：
Deshpande, Vikram;Nielsen, GunnIaligur Petur;Rosenberg, Andrew E.
通讯作者：
Rosenberg, Andrew E.
影响因子：
20.3
作者：
Greenberg, P;Cox, C;Bennett, J
通讯作者：
Bennett, J
影响因子：
50.3
作者：
Taylor AM;Shih J;Ha G;Gao GF;Zhang X;Berger AC;Schumacher SE;Wang C;Hu H;Liu J;Lazar AJ;Cancer Genome Atlas Research Network;Cherniack AD;Beroukhim R;Meyerson M
通讯作者：
Meyerson M