PMID- 15507670
OWN - NLM
STAT- MEDLINE
DCOM- 20050422
LR  - 20181113
IS  - 1525-1578 (Print)
IS  - 1525-1578 (Linking)
VI  - 6
IP  - 4
DP  - 2004 Nov
TI  - Intratumoral patterns of clonal evolution in meningiomas as defined by multicolor 
      interphase fluorescence in situ hybridization (FISH): is there a relationship 
      between histopathologically benign and atypical/anaplastic lesions?
PG  - 316-25
AB  - Meningiomas are cytogenetically heterogeneous tumors in which chromosome gains 
      and losses frequently occur. Based on the intertumoral cytogenetic heterogeneity 
      of meningiomas, hypothetical models of clonal evolution have been proposed in 
      these tumors which have never been confirmed at the intratumoral cell level. The 
      aim of this study was to establish the intratumoral patterns of clonal evolution 
      associated with chromosomal instability in individual patients as a way to 
      establish tumor progression pathways in meningiomas and their relationship with 
      tumor histopathology and behavior. A total of 125 meningioma patients were 
      analyzed at diagnosis. In all cases, multicolor interphase fluorescence in situ 
      hybridization (iFISH) studies were performed on fresh tumor samples for the 
      detection of quantitative abnormalities for 11 different chromosomes. In 
      addition, overall tumor cell DNA content was measured in parallel by flow 
      cytometry. iFISH studies were also performed in parallel on tissue sections in a 
      subset of 30 patients. FISH studies showed that 56 (45%) of the 125 cases 
      analyzed had a single tumor cell clone, all these cases corresponding to 
      histologically benign grade I tumors. In the remaining cases (55%) more than one 
      tumor cell clone was identified: two in 45 cases (36%), three in 19 (15%), and 
      four or more clones in five cases (4%). Overall, flow cytometric analysis of cell 
      DNA contents showed the presence of DNA aneuploidy in 44 of these cases (35%), 
      30% corresponding to DNA hyperdiploid and 5% to hypodiploid cases; from the DNA 
      aneuploid cases, 35 (28%) showed two clones and 9 (7%) had three or more clones. 
      A high degree of correlation (r >/= 0.89; P < 0.001) was found between FISH and 
      flow cytometry as regards the overall quantitative DNA changes detected with both 
      techniques, the former being more sensitive. Among the cases with chromosome 
      abnormalities, the earliest tumor cell clone observed was frequently 
      characterized by the loss of one or more chromosomes (64% of all meningiomas); 
      loss of either a single chromosome 22 or, less frequently, of a sex chromosome (X 
      or Y) and del (1p) was commonly found as the single initial cytogenetic 
      aberration (30%, 5%, and 5% of the cases, respectively). Interestingly, an 
      isolated loss of chromosome 22 was only found as the initial abnormality in one 
      out of 14 atypical/anaplastic meningiomas, while the same cytogenetic pattern was 
      present in the ancestral tumor cell clone of 32% of the benign tumors. 
      Cytogenetic patterns based on chromosome gains were found in the ancestral tumor 
      cell clone in 4% of the patients, 2% corresponding to tetraploid tumors. Overall, 
      cytogenetic evolution of the earliest tumor cell clones was frequently associated 
      with tetraploidization (31%). Our results show that meningiomas are genetically 
      heterogeneous tumors that display different patterns of numerical chromosome 
      changes, with the presence of more than one tumor cell clone detected in almost 
      half of the cases including all atypical/anaplastic cases. Interestingly, the 
      pathways of intratumoral clonal evolution observed in the benign tumors were 
      different from those observed in atypical/anaplastic meningiomas, suggesting that 
      the latter tumors might not always represent a more advanced stage of 
      histologically benign meningiomas.
FAU - Sayagues, Jose Maria
AU  - Sayagues JM
AD  - Servicio General de Citometria, Departamento de Medicina and Centro de 
      Investigaciones del Cancer, Universidad de Salamanca, Spain.
FAU - Tabernero, Maria Dolores
AU  - Tabernero MD
FAU - Maillo, Angel
AU  - Maillo A
FAU - Espinosa, Ana
AU  - Espinosa A
FAU - Rasillo, Ana
AU  - Rasillo A
FAU - Diaz, Pedro
AU  - Diaz P
FAU - Ciudad, Juana
AU  - Ciudad J
FAU - Lopez, Antonio
AU  - Lopez A
FAU - Merino, Marta
AU  - Merino M
FAU - Goncalves, Jesus Maria
AU  - Goncalves JM
FAU - Santos-Briz, Angel
AU  - Santos-Briz A
FAU - Morales, Francisco
AU  - Morales F
FAU - Orfao, Alberto
AU  - Orfao A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Mol Diagn
JT  - The Journal of molecular diagnostics : JMD
JID - 100893612
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cell Nucleus/metabolism
MH  - Chromosome Aberrations
MH  - Cytogenetics
MH  - DNA/analysis
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Male
MH  - Meningeal Neoplasms/*genetics/metabolism/*pathology
MH  - Meningioma/*genetics/*pathology
MH  - Microscopy, Fluorescence
MH  - Middle Aged
MH  - Models, Biological
MH  - Sex Chromosomes/ultrastructure
PMC - PMC1867491
EDAT- 2004/10/28 09:00
MHDA- 2005/04/23 09:00
PMCR- 2005/11/01
CRDT- 2004/10/28 09:00
PHST- 2004/10/28 09:00 [pubmed]
PHST- 2005/04/23 09:00 [medline]
PHST- 2004/10/28 09:00 [entrez]
PHST- 2005/11/01 00:00 [pmc-release]
AID - S1525-1578(10)60527-2 [pii]
AID - 04-0019 [pii]
AID - 10.1016/S1525-1578(10)60527-2 [doi]
PST - ppublish
SO  - J Mol Diagn. 2004 Nov;6(4):316-25. doi: 10.1016/S1525-1578(10)60527-2.