PMID- 12011257
OWN - NLM
STAT- MEDLINE
DCOM- 20020723
LR  - 20220330
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 15
IP  - 5
DP  - 2002 May
TI  - Differential involvement of protein 4.1 family members DAL-1 and NF2 in 
      intracranial and intraspinal ependymomas.
PG  - 526-31
AB  - Ependymomas are malignant CNS neoplasms with highly variable biologic behavior, 
      including a generally better prognosis for intraspinal tumors. Inactivation of 
      the NF2 gene on 22q12 and loss of its protein product, merlin, have been well 
      documented in subsets of meningiomas and ependymomas. DAL-1, a related tumor 
      suppressor and protein 4.1 family member on 18p11.3, has also been recently 
      implicated in meningioma pathogenesis, though its role in ependymoma remains 
      unknown. Therefore, we evaluated 27 ependymomas (12 intracranial and 15 spinal) 
      using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to 
      determine NF2/merlin and DAL-1/DAL-1 status at the DNA and protein levels. 
      Demonstrable NF2 and DAL-1 gene deletions were each detected in 6 (22%) 
      ependymomas. All 5 merlin losses by IHC occurred in spinal ependymomas (P =.047), 
      whereas 5 (71%) DAL-1-negative cases were intracranial (P =.185). The former 
      result is consistent with prior observations that NF2 mutations are generally 
      limited to spinal ependymomas. In contrast to meningiomas, simultaneous merlin 
      and DAL-1 losses were not encountered. Our findings suggest that (1) NF2 and 
      DAL-1 losses are involved in the pathogenesis of spinal and intracranial 
      ependymoma subsets, respectively and (2) given the number of cases with no 
      demonstrable losses, other cellular perturbations must also be critical for 
      tumori-genesis.
FAU - Singh, Pratima K
AU  - Singh PK
AD  - Department of Pathology, Washington University School of Medicine, St. Louis, 
      Missouri 63110-10963, USA.
FAU - Gutmann, David H
AU  - Gutmann DH
FAU - Fuller, Christine E
AU  - Fuller CE
FAU - Newsham, Irene F
AU  - Newsham IF
FAU - Perry, Arie
AU  - Perry A
LA  - eng
GR  - CA41520/CA/NCI NIH HHS/United States
GR  - CA7773000/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (EPB41L3 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Neurofibromin 2)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Brain Neoplasms/genetics/metabolism/*pathology
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Ependymoma/genetics/metabolism/*pathology
MH  - Female
MH  - Gene Deletion
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Male
MH  - Membrane Proteins/*biosynthesis/genetics
MH  - Microfilament Proteins
MH  - Middle Aged
MH  - Neurofibromin 2/*biosynthesis/genetics
MH  - Spinal Cord Neoplasms/genetics/metabolism/*pathology
MH  - Tumor Suppressor Proteins/*biosynthesis/genetics
EDAT- 2002/05/16 10:00
MHDA- 2002/07/24 10:01
CRDT- 2002/05/16 10:00
PHST- 2002/05/16 10:00 [pubmed]
PHST- 2002/07/24 10:01 [medline]
PHST- 2002/05/16 10:00 [entrez]
AID - 10.1038/modpathol.3880558 [doi]
PST - ppublish
SO  - Mod Pathol. 2002 May;15(5):526-31. doi: 10.1038/modpathol.3880558.