Department of Ophthalmology, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, University Hospital "Sveti Duh", Zagreb, Croatia.
Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
Hum Genomics. 2023 Sep 1;17(1):82. doi: 10.1186/s40246-023-00529-w.
This review presents current knowledge on the molecular biology of retinoblastoma (RB). Retinoblastoma is an intraocular tumor with hereditary and sporadic forms. 8,000 new cases of this ocular malignancy of the developing retina are diagnosed each year worldwide. The major gene responsible for retinoblastoma is RB1, and it harbors a large spectrum of pathogenic variants. Tumorigenesis begins with mutations that cause RB1 biallelic inactivation preventing the production of functional pRB proteins. Depending on the type of mutation the penetrance of RB is different. However, in small percent of tumors additional genes may be required, such as MYCN, BCOR and CREBBP. Additionally, epigenetic changes contribute to the progression of retinoblastoma as well. Besides its role in the cell cycle, pRB plays many additional roles, it regulates the nucleosome structure, participates in apoptosis, DNA replication, cellular senescence, differentiation, DNA repair and angiogenesis. Notably, pRB has an important role as a modulator of chromatin remodeling. In recent years high-throughput techniques are becoming essential for credible biomarker identification and patient management improvement. In spite of remarkable advances in retinoblastoma therapy, primarily in high-income countries, our understanding of retinoblastoma and its specific genetics still needs further clarification in order to predict the course of this disease and improve therapy. One such approach is the tumor free DNA that can be obtained from the anterior segment of the eye and be useful in diagnostics and prognostics.
这篇综述介绍了视网膜母细胞瘤（RB）的分子生物学的现有知识。视网膜母细胞瘤是一种眼内肿瘤，具有遗传性和散发性两种形式。全球每年新诊断出 8000 例这种发育中视网膜的眼部恶性肿瘤。导致视网膜母细胞瘤的主要基因是 RB1，它携带有大量的致病性变异。肿瘤发生始于导致 RB1 双等位基因失活的突变，从而阻止功能性 pRB 蛋白的产生。根据突变的类型，RB 的外显率不同。然而，在小部分肿瘤中，可能还需要其他基因，如 MYCN、BCOR 和 CREBBP。此外，表观遗传变化也有助于视网膜母细胞瘤的进展。除了在细胞周期中的作用外，pRB 还具有许多其他作用，它调节核小体结构，参与细胞凋亡、DNA 复制、细胞衰老、分化、DNA 修复和血管生成。值得注意的是，pRB 作为染色质重塑调节剂具有重要作用。近年来，高通量技术对于可信生物标志物的识别和患者管理的改善变得至关重要。尽管在视网膜母细胞瘤治疗方面取得了显著进展，尤其是在高收入国家，但为了预测这种疾病的进程并改善治疗效果，我们对视网膜母细胞瘤及其特定遗传学的理解仍需要进一步阐明。一种这样的方法是可以从前节眼液中获得的无肿瘤 DNA，它可用于诊断和预后。
