کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2121174 1085771 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Loss of photoreceptorness and gain of genomic alterations in retinoblastoma reveal tumor progression
ترجمه فارسی عنوان
از دست دادن جذب نور و افزایش تغییرات ژنومی در رتینوبلاستوما، پیشرفت تومور را نشان می دهد
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
چکیده انگلیسی


• RB1−/− retinoblastomas display highly differential gene expression signatures.
• Copy number alterations are strongly associated with gene expression differences.
• Gene expression and copy number differences reflect gradual tumor progression.

BackgroundRetinoblastoma is a pediatric eye cancer associated with RB1 loss or MYCN amplification (RB1+/+MYCNA). There are controversies concerning the existence of molecular subtypes within RB1−/− retinoblastoma. To test whether these molecular subtypes exist, we performed molecular profiling.MethodsGenome-wide mRNA expression profiling was performed on 76 primary human retinoblastomas. Expression profiling was complemented by genome-wide DNA profiling and clinical, histopathological, and ex vivo drug sensitivity data.FindingsRNA and DNA profiling identified major variability between retinoblastomas. While gene expression differences between RB1+/+MYCNA and RB1−/− tumors seemed more dichotomous, differences within the RB1−/− tumors were gradual. Tumors with high expression of a photoreceptor gene signature were highly differentiated, smaller in volume and diagnosed at younger age compared with tumors with low photoreceptor signature expression. Tumors with lower photoreceptor expression showed increased expression of genes involved in M-phase and mRNA and ribosome synthesis and increased frequencies of somatic copy number alterations.InterpretationMolecular, clinical and histopathological differences between RB1−/− tumors are best explained by tumor progression, reflected by a gradual loss of differentiation and photoreceptor expression signature. Since copy number alterations were more frequent in tumors with less photoreceptorness, genomic alterations might be drivers of tumor progression.Research in contextRetinoblastoma is an ocular childhood cancer commonly caused by mutations in the RB1 gene. In order to determine optimal treatment, tumor subtyping is considered critically important. However, except for very rare retinoblastomas without an RB1 mutation, there are controversies as to whether subtypes of retinoblastoma do exist. Our study shows that retinoblastomas are highly diverse but rather than reflecting distinct tumor types with a different etiology, our data suggests that this diversity is a result of tumor progression driven by cumulative genetic alterations. Therefore, retinoblastomas should not be categorized in distinct subtypes, but be described according to their stage of progression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: EBioMedicine - Volume 2, Issue 7, July 2015, Pages 660–670
نویسندگان
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