Table 1 Genetic, transcriptomic, epigenetic and proteomic changes observed in retinoblastoma

Genes

RB1 [13, 16, 27, 31, 32, 35, 36]

Large spectrum of pathogenic variants, nonsense mutations prevalent; downregulated

MYCN [13, 16, 17, 48]

Amplifications, gains; upregulated

BCOR [16, 48]

Mutations or loss; nonsense variants that result in truncated protein; downregulated

CREBBP [48, 71, 74, 75]

Nonsense variants that result in truncated protein, downregulated

MDM4 [13, 55]

Gains (4‒10 copies); skipping of exons 6 or 9; upregulated

KIF14 [13, 51, 52]

Gains (4‒10 copies); upregulated

E2F3 [13, 51, 52]

Gains; upregulated

DEK [13, 70,71,72,73]

Gains; upregulated

OTX2 [16]

Amplification; upregulated

RBL2 [16], RASSF1A [65,66,67], MDMX [3, 13, 52, 70], CDH11 [13, 52, 70], nuclear protein 7 (NOL7) [54]

Loss; downregulated

MGMT [13, 16, 50, 57, 66, 67]

Epigenetic silencing

MLH1 [16, 66, 67]

Mutation

APOA1, GFAP, RBP3, CRABPs [3, 53, 54]

Dysregulated

CRB1, NUP205, IL8, IL6, MYC, SMAD3, UBE2C, NEK7 [28], SKP2, SOX2 [9, 53, 69,70,71,72,73], SOX4 [52], Survivin [3], MDM2 [3], CDKN2A (p16INK4A), TFRC [3, 6, 40, 53, 54, 65]

Overexpression

HIST1H4H, RELN, RPTOR, TERT, MSH3, TSC2, ARID1A, CDK4, BRAF, JAK1, ROCK1, ARHGAP9, DRAIC [74, 75], CASP8 [66, 67], LMNB1 [3, 53, 54]

Downregulation

ABCA4, DAZAP1, Dab1 [55]

Aberrant splicing

TP53, CDH13, GATA5, CHFR, TP73, IGSF4 [50]

Deletions

Chromosomal aberrations

1q, 2p, 6p [49]

Gains

13q, 16q14 [49]

Losses

lncRNAs

BANCR, AFAP1-AS1, NEAT1, XIST, ANRIL, PlncRNA-1, HOTAIR, PANDAR, DANCR, THOR [59]

Differentially expressed

miRNAs

miR-216a, miR-217, let-7a, let-7i, let-7f, miR-9, miR-92a, miR-99b, miR-3613, miR486-3p and miR-532 [59,60,61]

Downregulated

miR-103, miR-142-5b, miR-106b, miR-143, miR-148b, miR-17, miR-16, miR-183, miR-182, miR-19a, miR-18a, miR-29a, miR-29b, miR-29c, miR-20a, miR-30b, miR-30d, miR-34a, miR-494, miR-378, miR-513, miR-513–1, miR-513–2, miR-518c, miR-96 [59,60,61]

Upregulated

miR-320, let-7e, and miR-21 [17]

Dysregulated in plasma of Rb patients

miR-20a, miR-373, miR-125b, let7a, let-7b, let-7c, miR-25, and miR-18a [60]

Differentially expressed during progression

miR181b, miR30c-2, miR125a3p, miR497, and miR491-3p [59]

Hypoxia-regulated miRNAs

Epigenetic alterations

RB1, MGMT, RASSF1A, CASP8, MLH1, CDKN2A/p16INK4A, VHL, LDHA, RUNX3, APC2, PAX5, EZH2, SKY, DNMT1a, DNMT3a, HELLS protein, PLK1, HMGA2,T3A, MSH6, CD44, PAX5, GATA5, TP53, GSTP1, CDK1, BUB1, CCNB2, CCNB1, TOP2A, RRM2, KIF11, KIF20A, NDC80, TTK [50, 63, 65,66,67]

Genes with aberrant methylation of promoters

H2AFX, SIRT1, BRD4, WNK1, CDK1 [52, 65]

Hyperphosphorylated

Proteomic profiling

IGF2BP1, SOX4, B7H3, chromogranin A, Rac GTPase-activating protein 1, fetuin A, midkine, LRP1 COMP, TGB3, TLN, FLNA, OGN, A1BG, Serpin A1, ORM2, LRG1, CHI3L1, transferrin, TFRC (Transferrin Receptor), alpha-crystallin A, CRABP2 [3, 52, 76,77,78]

Upregulated

PEDF, nucleolin (NCL) [76,77,78]

Downregulated