PMID- 19280657
OWN - NLM
STAT- MEDLINE
DCOM- 20090730
LR  - 20090504
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Linking)
VI  - 30
IP  - 5
DP  - 2009 May
TI  - Detection of mosaic RB1 mutations in families with retinoblastoma.
PG  - 842-51
LID - 10.1002/humu.20940 [doi]
AB  - The RB1 gene mutation detection rate in 1,020 retinoblastoma families was 
      increased by the use of highly sensitive allele specific-PCR (AS-PCR) to detect 
      low-level mosaicism for 11 recurrent RB1 CGA>TGA nonsense mutations. For 
      bilaterally affected probands, AS-PCR increased the RB1 mutation detection 
      sensitivity from 92.6% to 94.8%. Both RB1 oncogenic changes were detected in 
      92.7% of sporadic unilateral tumors (357/385); 14.6% (52/357) of unilateral 
      probands with both tumor mutations identified carried one of the tumor mutations 
      in blood. Mosaicism was evident in 5.5% of bilateral probands (23 of 421), in 
      3.8% of unilateral probands (22 of 572), and in one unaffected mother of a 
      unilateral proband. Half of the mosaic mutations were only detectable by AS-PCR 
      for the 11 recurrent CGA>TGA mutations, and not by standard sequencing. This 
      suggests that significant numbers of low-level mosaics with other classes of RB1 
      mutations remain unidentified by current technology. We show that the use of 
      linkage analysis in a two-generation retinoblastoma family resulted in the 
      erroneous conclusion that a child carried the parental mutation, because the 
      founder parent was mosaic for the RB1 mutation. Of 142 unaffected parental pairs 
      tested, only one unaffected parent of a proband (0.7%) showed somatic mosaicism 
      for the proband's mutation, in contrast to an overall 4.5% somatic mosaicism rate 
      for retinoblastoma probands, suggesting that mosaicism for an RB1 mutation is 
      highly likely to manifest as retinoblastoma.
CI  - Copyright 2009 Wiley-Liss, Inc.
FAU - Rushlow, Diane
AU  - Rushlow D
AD  - Retinoblastoma Solutions, Toronto Western Hospital, Toronto, Ontario, Canada.
FAU - Piovesan, Beata
AU  - Piovesan B
FAU - Zhang, Katherine
AU  - Zhang K
FAU - Prigoda-Lee, Nadia L
AU  - Prigoda-Lee NL
FAU - Marchong, Mellone N
AU  - Marchong MN
FAU - Clark, Robin D
AU  - Clark RD
FAU - Gallie, Brenda L
AU  - Gallie BL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (Retinoblastoma Protein)
SB  - IM
MH  - Base Sequence
MH  - DNA Mutational Analysis
MH  - Female
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mosaicism
MH  - Mutation/*genetics
MH  - Polymerase Chain Reaction
MH  - Retinoblastoma/*genetics
MH  - Retinoblastoma Protein/*genetics
EDAT- 2009/03/13 09:00
MHDA- 2009/07/31 09:00
CRDT- 2009/03/13 09:00
PHST- 2009/03/13 09:00 [entrez]
PHST- 2009/03/13 09:00 [pubmed]
PHST- 2009/07/31 09:00 [medline]
AID - 10.1002/humu.20940 [doi]
PST - ppublish
SO  - Hum Mutat. 2009 May;30(5):842-51. doi: 10.1002/humu.20940.