TY  - CHAP
M1  - Book, Section
TI  - Retinoblastoma
A1  - Newsham, Irene F.
A1  - Hadjistilianou, Theodora
A1  - Cavenee, Webster K.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
Y1  - 2019
N1  - 10.1036/ommbid.337
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Retinoblastoma  is  the  most  common  intraocular  malignancy  in  children,  with  a  worldwide  incidence  between  1  in  13,500  and  1  in  25,000  live  births.  The  presenting  signs  and  symptoms  include  leukokoria,  strabismus,  low-vision  orbital  cellulitis,  unilateral  mydriasis,  and  heterochromia.  The  disease  can  be  unifocal  or  multifocal  and  unilateral  or  bilateral.  The  average  age  of  diagnosis  is  12  months  for  bilateral  and  18  months  for  unilateral  cases,  and  90  percent  of  affected  individuals  are  diagnosed  before  age  3  years.  Unusual  manifestations  of  this  disease  include  late  onset  retinoblastoma,  13q-deletion  syndrome,  retinoma,  trilateral  retinoblastoma,  and  second-site  primary  tumors,  including  osteosarcoma,  Ewing  sarcoma,  leukemia,  and  lymphoma.Early  diagnosis  and  treatment  are  of  primary  importance  in  the  survival  of  retinoblastoma  patients.  A  variety  of  diagnostic  approaches  are  used,  including  computed  tomography  (CT),  magnetic  resonance  imaging  (MRI),  ultrasonography,  and  fine-needle  aspiration  biopsy  (FNAB).  Each  has  advantages,  and  when  used  in  combination,  they  can  establish  the  proper  disease  classification.  Effective  methods  for  the  treatment  of  retinoblastoma  tumors  include  enucleation,  external-beam  irradiation,  episcleral  plaques,  xenon  arc  and  argon  laser  photocoagulation,  cryotherapy,  and  chemotherapy.  The  choice  of  treatment  depends  on  several  factors,  such  as  multifocal  or  unifocal  disease,  site  and  size  of  the  tumor,  diffuse  or  focal  vitreous  seeding,  age  at  diagnosis,  and  histopathologic  findings.Retinoblastoma  has  served  as  the  prototypic  example  of  a  genetic  predisposition  to  cancer.  It  is  estimated  that  60  percent  of  cases  are  nonhereditary  and  unilateral,  15  percent  are  hereditary  and  unilateral,  and  25  percent  are  hereditary  and  bilateral.  A  model  encompassing  these  findings  suggests  a  requirement  for  as  few  as  two  stochastic  mutational  events  for  tumor  formation.  The  first  of  these  events  can  be  inherited  through  the  germ  line  or  can  be  somatically  acquired,  whereas  the  second  occurs  somatically  in  either  case  and  leads  to  a  tumor  that  is  doubly  defective  at  the  retinoblastoma  locus.  Cytogenetic  analyses  have  demonstrated  the  involvement  of  a  genetic  alteration  in  a  gene  for  negative  growth  regulation  at  chromosome  band  13q14.  This  model  has  been  tested  and  confirmed  using  restriction-fragment-length  polymorphisms  (RFLP)  for  loci  on  chromosome  13.  These  studies  have  shown  that  the  second  wild-type  retinoblastoma  allele  may  be  lost  by  several  somatic  mutational  mechanisms,  including  mitotic  nondisjunction  with  loss  of  the  wild-type  chromosome,  mitotic  nondisjunction  with  duplication  of  the  mutant  chromosome,  mitotic  recombination  between  the  RB1  locus  and  the  centromere,  and  other  regionalized  events,  such  as  deletion  and  point  mutation.The  200-kb  genomic  locus  for  RB1  has  been  isolated,  and  its  exon/intron  structure  has  been  characterized.  Current  molecular  technology  has  allowed  the  identification  of  a  variety  of  aberrations  in  this  locus  in  retinoblastoma  patients  and  their  tumors  at  the  DNA,  RNA,  and  protein  levels.  RB1  alterations  also  have  been  detected  in  a  variety  of  clinically  related  second-site  primary  tumors  and  nonrelated  tumors,  including  osteosarcoma,  breast  carcinoma,  and  small-cell  lung  carcinoma.  The  ability  to  detect  mutations  in  RB1  coupled  with  the  isolation  of  polymorphic  sequences  within  the  gene  locus,  has  further  extended  the  prenatal  risk  assessment  for  this  pediatric  tumor.The  RB1  locus  is  transcribed  into  a  4.7-kb  mRNA  with  a  corresponding  protein  product  of  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
M3  - doi: 10.1036/ommbid.337
Y2  - 2024/04/23
UR  - ommbid.mhmedical.com/content.aspx?aid=1181414880
ER  -