Lancet Oncol：MYCN癌基因扩增水平或可用于视网膜母细胞瘤诊断

2013-03-22 echo1166 丁香园

MYCN癌基因视网膜母细胞瘤

视网膜母细胞瘤是发生在儿童期的视网膜肿瘤。既往的研究显示RB1视网膜母细胞瘤抑制基因的两个等位基因都出现突变是疾病发生的始发因素。来自加拿大University Health Network的Diane E Rushlow等试图确定没有RB1突变的非家族性的视网膜母细胞瘤的特征。他们的研究结果发表在Lancet Oncol 3月的在线期刊上。研究者纳入了1068名单侧非家族性视网膜母细胞瘤患者，并

视网膜母细胞瘤是发生在儿童期的视网膜肿瘤。既往的研究显示RB1视网膜母细胞瘤抑制基因的两个等位基因都出现突变是疾病发生的始发因素。来自加拿大University Health Network的Diane E Rushlow等试图确定没有RB1突变的非家族性的视网膜母细胞瘤的特征。他们的研究结果发表在Lancet Oncol 3月的在线期刊上。
研究者纳入了1068名单侧非家族性视网膜母细胞瘤患者，并将不存在RB1突变（RB1+/+）的肿瘤患者和RB1两个等位基因都出现突变（RB1–/–)的肿瘤患者进行了比较。同时，研究者也分析了他们的基因拷贝数、RB1基因表达和蛋白功能、视网膜基因表达、组织学特征和临床特征。
在1068名单侧视网膜母细胞瘤患者中，仅有29人（2.7%）无RB1突变（RB1+/+）。在这29名RB1+/+的患者中，都存在高水平的MYCN癌基因扩增（28–121拷贝；RB1+/+MYCNA），而在93名RB1-/-的视网膜母细胞瘤患者中，没有一人表现出MYCN的扩增，上述差异具有显著统计学意义。与RB1-/-的肿瘤相比，RB1+/+MYCNA肿瘤表达的功能性RB1蛋白的特征表现为总体基因拷贝数变化更少，其表现出独体的侵袭性的组织学特征。在一名RB1+/+MYCNA视网膜母细胞瘤患者中MYCNA扩增表现为拷贝数的变化。在17名RB1+/+MYCNA视网膜母细胞瘤患者中，其确诊时的平均年龄为4.5月（IQR 3.5-10），而79名非家族性单侧RB1-/-视网膜母细胞瘤患者确诊时的平均年龄为24月（15-37）。
MYCN癌基因扩增或许是无RB1基因突变的视网膜母细胞瘤患者病变的始发因素。单侧RB1+/+MYCNA视网膜母细胞瘤因具有独特的组织学特征，仅有少数的基因拷贝数发生变化，在早期就能得到诊断。
与视网膜母细胞瘤相关的拓展阅读：

Background
Retinoblastoma is the childhood retinal cancer that defined tumour-suppressor genes. Previous work shows that mutation of both alleles of the RB1 retinoblastoma suppressor gene initiates disease. We aimed to characterise non-familial retinoblastoma tumours with no detectable RB1 mutations.
Methods
Of 1068 unilateral non-familial retinoblastoma tumours, we compared those with no evidence of RB1 mutations (RB1+/+) with tumours carrying a mutation in both alleles (RB1−/−). We analysed genomic copy number, RB1 gene expression and protein function, retinal gene expression, histological features, and clinical data.
Findings
No RB1 mutations (RB1+/+) were reported in 29 (2·7%) of 1068 unilateral retinoblastoma tumours. 15 of the 29 RB1+/+ tumours had high-level MYCN oncogene amplification (28—121 copies; RB1+/+MYCNA), whereas none of 93 RB1−/− primary tumours tested showed MYCN amplification (p<0·0001). RB1+/+MYCNA tumours expressed functional RB1 protein, had fewer overall genomic copy-number changes in genes characteristic of retinoblastoma than did RB1−/− tumours, and showed distinct aggressive histological features. MYCN amplification was the sole copy-number change in one RB1+/+MYCNA retinoblastoma. One additional MYCNA tumour was discovered after the initial frequencies were determined, and this is included in further analyses. Median age at diagnosis of the 17 children with RB1+/+MYCNA tumours was 4·5 months (IQR 3·5—10), compared with 24 months (15—37) for 79 children with non-familial unilateral RB1−/− retinoblastoma.
Interpretation
Amplification of the MYCN oncogene might initiate retinoblastoma in the presence of non-mutated RB1 genes. These unilateral RB1+/+MYCNA retinoblastomas are characterised by distinct histological features, only a few of the genomic copy-number changes that are characteristic of retinoblastoma, and very early age of diagnosis.
Funding
National Cancer Institute—National Institutes of Health, Canadian Institutes of Health Research, German Research Foundation, Canadian Retinoblastoma Society, Hyland Foundation, Toronto Netralaya and Doctors Lions Clubs, Ontario Ministry of Health and Long Term Care, UK-Essen, and Foundations Avanti-STR and KiKa.

作者：echo1166



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