PMID- 23233862
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20121213
LR  - 20211021
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 3
DP  - 2012
TI  - More epigenetic hits than meets the eye: microRNAs and genes associated with the 
      tumorigenesis of retinoblastoma.
PG  - 284
LID - 10.3389/fgene.2012.00284 [doi]
LID - 284
AB  - Retinoblastoma (RB), a childhood neoplasia of the retinoblasts, can occur 
      unilaterally or bilaterally, with one or multiple foci per eye. RB is associated 
      with somatic loss of function of both alleles of the tumor suppressor gene RB1. 
      Hereditary forms emerge due to germline loss of function mutations in RB1 
      alleles. RB has long been the prototypic "model" cancer ever since Knudson's 
      "two-hit" hypothesis. However, a simple two-hit model for RB is challenged by an 
      increasing number of studies documenting additional hits that contribute to RB 
      development. Here we review the genetics and epigenetics of RB with a focus on 
      the role of small non-coding RNAs (microRNAs) and on novel findings indicating 
      the relevance of DNA methylation in the development and prognosis of this 
      neoplasia. Studies point to an elaborated landscape of genetic and epigenetic 
      complexity, in which a number of events and pahtways play crucial roles in the 
      origin and prognosis of RB. These include roles for microRNAs, inprinted loci, 
      and parent-of-origin contributions to RB1 regulation and RB progression. This 
      complexity is also manifested in the structure of the RB1 locus itself: it 
      includes numerous repetitive DNA segments and retrotransposon insertion elements, 
      some of which are actively transcribed from the RB1 locus. Altogether, we 
      conclude that RB1 loss of function represents the tip of an iceberg of events 
      that determine RB development, progression, severity, and disease risk. 
      Comprehensive assessment of personalized RB risk will require genetic and 
      epigenetic evaluations beyond RB1 protein coding sequences.
FAU - Reis, Adriana H O
AU  - Reis AH
AD  - Genetics Program, Instituto Nacional de Cancer Rio de Janeiro, Brazil.
FAU - Vargas, Fernando R
AU  - Vargas FR
FAU - Lemos, Bernardo
AU  - Lemos B
LA  - eng
PT  - Journal Article
DEP - 20121207
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC3516829
OTO - NOTNLM
OT  - Rb1
OT  - childhood cancer
OT  - imprinting
OT  - methylation
OT  - retinoblastoma
OT  - risk assessment
OT  - tumor suppressor
OT  - two-hit hypothesis
EDAT- 2012/12/13 06:00
MHDA- 2012/12/13 06:01
PMCR- 2012/12/07
CRDT- 2012/12/13 06:00
PHST- 2012/10/03 00:00 [received]
PHST- 2012/11/21 00:00 [accepted]
PHST- 2012/12/13 06:00 [entrez]
PHST- 2012/12/13 06:00 [pubmed]
PHST- 2012/12/13 06:01 [medline]
PHST- 2012/12/07 00:00 [pmc-release]
AID - 10.3389/fgene.2012.00284 [doi]
PST - epublish
SO  - Front Genet. 2012 Dec 7;3:284. doi: 10.3389/fgene.2012.00284. eCollection 2012.