PMID- 15066320
OWN - NLM
STAT- MEDLINE
DCOM- 20040630
LR  - 20061115
IS  - 0165-4608 (Print)
IS  - 0165-4608 (Linking)
VI  - 150
IP  - 2
DP  - 2004 Apr 15
TI  - Chromosome 11 monosomy in conjunction with a mutated SDHD initiation codon in 
      nonfamilial paraganglioma cases.
PG  - 128-35
AB  - Paragangliomas of the head and neck region are a group of rare, usually benign, 
      slow-growing tumors developing from paraganglionic chemoreceptors in most 
      patients. Mutations in a subunit of the mitochondrial enzyme II complex 
      (succinate dehydrogenase [SDHD]) were shown to be responsible for the formation 
      of paragangliomas. In addition, loss of heterozygosity (LOH) on chromosome 11, 
      mainly in 11q23 (PGL1), was observed recently. We analyzed DNA derived from tumor 
      sections of three unrelated paraganglioma patients (one case with multiple 
      paragangliomas, two cases with single tumors; all of them sporadic cases) for 
      mutations in the SDHD gene by direct sequencing. Microsatellite-based LOH was 
      performed, and events of chromosomal loss were validated by fluorescence in situ 
      hybridization (FISH) on paraffin-embedded tumor and normal tissue by using 
      centromeric satellite DNA. Sequence analysis revealed mutations in SDHD exon 1 in 
      all patients, affecting the initiation codon (M1V). Another alteration was 
      detected in exon 2 but was lacking in tumor DNA and therefore classified as 
      polymorphism (H50R). LOH and FISH analyses demonstrated partial/total monosomy 
      for chromosome 11 in the tumor samples tested. A common genetic mechanism appears 
      to be the pathophysiologic basis for sporadic tumor development because the 
      proposed two-hit model comprising both LOH and point mutation is manifest in our 
      patients. Loss of chromosome 11 regions, including the deletion of PGL1 and PGL2 
      loci, may result in a more severe phenotype, as exemplified by the development of 
      multiple tumors in one of the patients.
FAU - Riemann, Kathrin
AU  - Riemann K
AD  - Institute of Pathology, University of Tubingen, Wilhelmstrasse 27, 72074 
      Tubingen, Germany.
FAU - Sotlar, Karl
AU  - Sotlar K
FAU - Kupka, Susan
AU  - Kupka S
FAU - Braun, Simone
AU  - Braun S
FAU - Zenner, Hans-Peter
AU  - Zenner HP
FAU - Preyer, Serena
AU  - Preyer S
FAU - Pfister, Markus
AU  - Pfister M
FAU - Pusch, Carsten M
AU  - Pusch CM
FAU - Blin, Nikolaus
AU  - Blin N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Genet Cytogenet
JT  - Cancer genetics and cytogenetics
JID - 7909240
RN  - 0 (Codon, Initiator)
RN  - 0 (Genetic Markers)
RN  - EC 1.3.5.1 (Electron Transport Complex II)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Base Sequence
MH  - *Chromosome Deletion
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 11/*genetics
MH  - Codon, Initiator/*genetics
MH  - Electron Transport Complex II/*genetics
MH  - Exons/genetics
MH  - Female
MH  - Genetic Markers
MH  - Humans
MH  - Male
MH  - Paraganglioma/*genetics
MH  - Polymorphism, Single Nucleotide
EDAT- 2004/04/07 05:00
MHDA- 2004/07/01 05:00
CRDT- 2004/04/07 05:00
PHST- 2003/07/07 00:00 [received]
PHST- 2003/10/10 00:00 [revised]
PHST- 2003/10/17 00:00 [accepted]
PHST- 2004/04/07 05:00 [pubmed]
PHST- 2004/07/01 05:00 [medline]
PHST- 2004/04/07 05:00 [entrez]
AID - S0165460803004667 [pii]
AID - 10.1016/j.cancergencyto.2003.10.013 [doi]
PST - ppublish
SO  - Cancer Genet Cytogenet. 2004 Apr 15;150(2):128-35. doi: 
      10.1016/j.cancergencyto.2003.10.013.