- Email: [email protected]
Unusual numeric increase of chromosome 22 in a human glioma cell - line and its biological properties
250
Abstracts
85 LOCALIZATION TRANSLOCATION
OF
THE
MENINGIOMA
TUMOR
SUPPRESSOR
GENE
USING
A
R o n a l d H. L e k a n n e D e p r e z , * N i c o l e A. G r o e n , * N i c k A. v a n B i e z e n , * A. Hagemeyer,+ Ellen van Drunen,+ Jan-Willem Koper,# C.J.J. A v e z a a t , $ D. B o o t s m a , + a n d E l l e n C. Z w a r t h o f f * *Department of P a t h o l o g y , +Cellbiology and Genetics, M e d i c i n e III, $ N e u r o s u r g e r y , Erasmus University, P.O. 3000 DR R o t t e r d a m . T h e N e t h e r l a n d s .
#Internal Box 1738,
M e n i n g i o m a p r e s u m a b l y d e v e l o p s w h e n b o t h a l l e l e s of a s u p p r e s s o r g e n e on c h r o m o s o m e 22 are i n a c t i v a t e d . C y t o g e n e t i c a n a l y s i s of m e n i n g i o m a c e l l s f r o m one p a t i e n t s h o w e d in all c e l l s an a b n o r m a l s t e m line: 45, XY, -i, 4p+, 22q-, 22q+. T h e 22q+ m a r k e r a p p e a r e d as a d i c e n t r i c : 22 p t e r ,qll::ipll--gqter. T h e 22q- c h r o m o s o m e appeared to have lost sequences distal from band qll. To investigate these rearrangements further, human-hamster somatic cell h y b r i d s w e r e c o n s t r u c t e d t h a t s e g r e g a t e d the 22q- and 4p+ chromosomes. We found that sequences from 22q d i s t a l to the breakpoint were translocated on 4p+ a n d r e c i p r o c a l l y sequences from 4p w e r e translocated to 22q-, demonstrating a balanced t r a n s l o c a t i o n t(4;22) (pl6;qll). D N A m a r k e r s l o c a t e d on 4p and 22q w e r e u s e d to d e f i n e the b r e a k p o i n t s of t h e t r a n s l o c a t i o n s . The breakpoints on b o t h m a r k e r s 22q+ and 22q- w e r e l o c a t e d b e t w e e n D 2 2 S I a n d t h e m y o g l o b i n l o c u s on c h r o m o s o m e 22. We h y p o t h e s i z e t h a t the s u p p r e s s o r g e n e i n v o l v e d in m e n i n g i o m a is i n a c t i v a t e d or d e l e t e d in the 22q+ m a r k e r and t h a t t h e o t h e r a l l e l e of the g e n e is i n a c t i v a t e d as a r e s u l t of the b a l a n c e d t r a n s l o c a t i o n t(4;22). 66
Cytogenetic studies and RFLP-analysis of derived from patients with neurofibromatosis
various 1
H i l d e g a r d K e h r e r , T h o m a s Fink, I n g r i d A l b r e c h t , Winfrid Krone A b t e i l u n g H u m a n g e n e t i k , U n i v e r s i t 6 t Ulm, G e r m a n y
cell
Dieter
types
Kaufmann,
C a f e - a u - l a i t m a c u l e s (CALM), L i s c h n o d u l e s , a n d a x i l l a r y f r e c k ling i n d i c a t e t h a t m e l a n o c y t e s (MC) are a f f e c t e d by the u n d e r l y i n g g e n e d e f e c t of NF i. C o m p a r a t i v e c y t o g e n e t i c s t u d i e s w e r e t h e r e f o r e p e r f o r m e d w i t h c u l t u r e d m e l a n o c y t e s f r o m the e p i d e r m i s of h e a l t h y d o n o r s (I; n=5); f r o m t h e skin o v e r l y i n g n e u r o f i b r o mas of NF 1 p a t i e n t s III; n=6), and f r o m C A L M of t h e s e p a t i e n t s (III; n=4). Higher average r a t e s of n u m e r i c a l and structural changes, breaks, premature centromer division and d e c o n d e n s e d c h r o m o s o m e s w e r e f o u n d in MC f r o m II and III as c o m p a r e d w i t h t h o s e f r o m I. No c h a r a c t e r i s t i c c h r o m o s o m a l a n o m a l y w a s s e e n in NF 1 MC. D N A f r o m M C (II a n d III) and f r o m n e u r o f i b r o m a - d e r i v e d perineurial cells and fibroblasts, respectively, was analysed for 13 R F L P s localized on c h r o m o s o m e 17. All patients were informative at l e a s t at t h r e e of t h e s e loci. None of t h e s e samples exhibited loss of h e t e r o z y g o s i t y . Since half of the p r o b e s u s e d d e t e c t R F L P s in the i m m e d i a t e v i c i n i t y of the NF 1 locus, d e l e t i o n s s p a n n i n g l a r g e r s e g m e n t s a r o u n d t h i s locus do not s e e m to be a v e r y f r e q u e n t c a u s e of the b e n i g n d i s s e m i n a t e d l e s i o n s in NF i.
Abstracts
85 LOCALIZATION TRANSLOCATION
OF
THE
MENINGIOMA
TUMOR
SUPPRESSOR
GENE
USING
A
R o n a l d H. L e k a n n e D e p r e z , * N i c o l e A. G r o e n , * N i c k A. v a n B i e z e n , * A. Hagemeyer,+ Ellen van Drunen,+ Jan-Willem Koper,# C.J.J. A v e z a a t , $ D. B o o t s m a , + a n d E l l e n C. Z w a r t h o f f * *Department of P a t h o l o g y , +Cellbiology and Genetics, M e d i c i n e III, $ N e u r o s u r g e r y , Erasmus University, P.O. 3000 DR R o t t e r d a m . T h e N e t h e r l a n d s .
#Internal Box 1738,
M e n i n g i o m a p r e s u m a b l y d e v e l o p s w h e n b o t h a l l e l e s of a s u p p r e s s o r g e n e on c h r o m o s o m e 22 are i n a c t i v a t e d . C y t o g e n e t i c a n a l y s i s of m e n i n g i o m a c e l l s f r o m one p a t i e n t s h o w e d in all c e l l s an a b n o r m a l s t e m line: 45, XY, -i, 4p+, 22q-, 22q+. T h e 22q+ m a r k e r a p p e a r e d as a d i c e n t r i c : 22 p t e r ,qll::ipll--gqter. T h e 22q- c h r o m o s o m e appeared to have lost sequences distal from band qll. To investigate these rearrangements further, human-hamster somatic cell h y b r i d s w e r e c o n s t r u c t e d t h a t s e g r e g a t e d the 22q- and 4p+ chromosomes. We found that sequences from 22q d i s t a l to the breakpoint were translocated on 4p+ a n d r e c i p r o c a l l y sequences from 4p w e r e translocated to 22q-, demonstrating a balanced t r a n s l o c a t i o n t(4;22) (pl6;qll). D N A m a r k e r s l o c a t e d on 4p and 22q w e r e u s e d to d e f i n e the b r e a k p o i n t s of t h e t r a n s l o c a t i o n s . The breakpoints on b o t h m a r k e r s 22q+ and 22q- w e r e l o c a t e d b e t w e e n D 2 2 S I a n d t h e m y o g l o b i n l o c u s on c h r o m o s o m e 22. We h y p o t h e s i z e t h a t the s u p p r e s s o r g e n e i n v o l v e d in m e n i n g i o m a is i n a c t i v a t e d or d e l e t e d in the 22q+ m a r k e r and t h a t t h e o t h e r a l l e l e of the g e n e is i n a c t i v a t e d as a r e s u l t of the b a l a n c e d t r a n s l o c a t i o n t(4;22). 66
Cytogenetic studies and RFLP-analysis of derived from patients with neurofibromatosis
various 1
H i l d e g a r d K e h r e r , T h o m a s Fink, I n g r i d A l b r e c h t , Winfrid Krone A b t e i l u n g H u m a n g e n e t i k , U n i v e r s i t 6 t Ulm, G e r m a n y
cell
Dieter
types
Kaufmann,
C a f e - a u - l a i t m a c u l e s (CALM), L i s c h n o d u l e s , a n d a x i l l a r y f r e c k ling i n d i c a t e t h a t m e l a n o c y t e s (MC) are a f f e c t e d by the u n d e r l y i n g g e n e d e f e c t of NF i. C o m p a r a t i v e c y t o g e n e t i c s t u d i e s w e r e t h e r e f o r e p e r f o r m e d w i t h c u l t u r e d m e l a n o c y t e s f r o m the e p i d e r m i s of h e a l t h y d o n o r s (I; n=5); f r o m t h e skin o v e r l y i n g n e u r o f i b r o mas of NF 1 p a t i e n t s III; n=6), and f r o m C A L M of t h e s e p a t i e n t s (III; n=4). Higher average r a t e s of n u m e r i c a l and structural changes, breaks, premature centromer division and d e c o n d e n s e d c h r o m o s o m e s w e r e f o u n d in MC f r o m II and III as c o m p a r e d w i t h t h o s e f r o m I. No c h a r a c t e r i s t i c c h r o m o s o m a l a n o m a l y w a s s e e n in NF 1 MC. D N A f r o m M C (II a n d III) and f r o m n e u r o f i b r o m a - d e r i v e d perineurial cells and fibroblasts, respectively, was analysed for 13 R F L P s localized on c h r o m o s o m e 17. All patients were informative at l e a s t at t h r e e of t h e s e loci. None of t h e s e samples exhibited loss of h e t e r o z y g o s i t y . Since half of the p r o b e s u s e d d e t e c t R F L P s in the i m m e d i a t e v i c i n i t y of the NF 1 locus, d e l e t i o n s s p a n n i n g l a r g e r s e g m e n t s a r o u n d t h i s locus do not s e e m to be a v e r y f r e q u e n t c a u s e of the b e n i g n d i s s e m i n a t e d l e s i o n s in NF i.