Bell Diana, Raza Shaan M, Bell Achim H, Fuller Gregory N, DeMonte Franco
Department of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Virchows Arch. 2016 Oct;469(4):439-49. doi: 10.1007/s00428-016-1985-y. Epub 2016 Jul 11.
Fourteen skull base chordoma specimens and three normal specimens were microdissected from paraffin-embedded tissue. Pools of RNA from highly enriched preparations of these cell types were subjected to expression profiling using whole-transcriptome shotgun sequencing. Using strict criteria, 294 differentially expressed transcripts were found, with 28 % upregulated and 72 % downregulated. The transcripts were annotated using NCBI Entrez Gene and computationally analyzed with the Ingenuity Pathway Analysis program. From these significantly changed expressions, the analysis identified 222 cancer-related transcripts. These 294 differentially expressed genes and non-coding RNA transcripts provide here a set to specifically define skull base chordomas and to identify novel and potentially important targets for diagnosis, prognosis, and therapy of this cancer. Significance Genomic profiling to subtype skull base chordoma reveals potential candidates for specific biomarkers, with validation by IHC for selected candidates. The highly expressed developmental genes T, LMX1A, ZIC4, LHX4, and HOXA1 may be potential drivers of this disease.
从石蜡包埋组织中显微切割出14例颅底脊索瘤标本和3例正常标本。对这些细胞类型高度富集制剂的RNA样本进行全转录组鸟枪法测序，以进行表达谱分析。使用严格标准，发现294个差异表达转录本，其中28%上调，72%下调。使用NCBI Entrez Gene对这些转录本进行注释，并使用Ingenuity Pathway Analysis程序进行计算分析。通过这些显著变化的表达，分析鉴定出222个与癌症相关的转录本。这组294个差异表达基因和非编码RNA转录本可用于明确界定颅底脊索瘤，并为该癌症的诊断、预后和治疗识别新的潜在重要靶点。意义：对颅底脊索瘤进行基因组分析以确定亚型，揭示了特定生物标志物的潜在候选物，并通过免疫组化对选定候选物进行验证。高表达的发育基因T、LMX1A、ZIC4、LHX4和HOXA1可能是该疾病的潜在驱动因素。
