PMID- 10023947
OWN - NLM
STAT- MEDLINE
DCOM- 19990304
LR  - 20220419
IS  - 0140-6736 (Print)
IS  - 0140-6736 (Linking)
VI  - 353
IP  - 9146
DP  - 1999 Jan 2
TI  - Inactivation of ataxia telangiectasia mutated gene in B-cell chronic lymphocytic 
      leukaemia.
PG  - 26-9
AB  - BACKGROUND: Patients with the inherited disorder ataxia telangiectasia (A-T) have
      an increased susceptibility to lymphoid malignancies. In these patients mutations
      affect both alleles of the A-T gene (ATM). We have looked for mutations in the
      ATM gene in sporadic cases of B-cell chronic lymphocytic leukaemia (B-CLL).
      METHODS: 32 cases of B-CLL were analysed by restriction endonuclease
      fingerprinting to detect mutations within ATM. In six of the cases in which
      mutations were detected in tumour samples, germline DNA was screened to assess
      ATM carrier status. The samples in 20 cases were also studied by western blot for
      abnormal expression of ATM protein. FINDINGS: Expression of the ATM protein was
      impaired in eight (40%) of the 20 tumours analysed, being absent in three and
      decreased in five. Mutations within ATM were detected in six (18%) of the 32
      patients. These point mutations, deletions, and one insertion were distributed
      across the coding sequence of ATM. Germline mutations, which indicate ATM carrier
      status, were found in two of these six patients compared with a frequency within 
      the general population of below 1 in 200. INTERPRETATION: Abnormal expression of 
      ATM protein is a frequent finding in B-CLL. Although the precise function of this
      protein is unknown, it is thought to have a role in programmed cell death, a
      deficiency of which would fit with the characteristic phenotype of prolonged cell
      survival seen in B-CLL tumour cells. Our results also suggest that carriers of
      ATM mutations may be at a particular risk for the development of B-CLL and this
      may partly explain the known genetic susceptibility to this disease.
FAU - Stankovic, T
AU  - Stankovic T
AD  - CRC Institute for Cancer Studies, Medical School, University of Birmingham,
      Edgbaston, UK.
FAU - Weber, P
AU  - Weber P
FAU - Stewart, G
AU  - Stewart G
FAU - Bedenham, T
AU  - Bedenham T
FAU - Murray, J
AU  - Murray J
FAU - Byrd, P J
AU  - Byrd PJ
FAU - Moss, P A
AU  - Moss PA
FAU - Taylor, A M
AU  - Taylor AM
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Lancet
JT  - Lancet (London, England)
JID - 2985213R
RN  - 5J49Q6B70F (Vincristine)
RN  - 80168379AG (Doxorubicin)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - 9PHQ9Y1OLM (Prednisolone)
RN  - EC 3.1.21.- (DNA Restriction Enzymes)
RN  - VAP-cyclo protocol
SB  - IM
CIN - Lancet. 1999 Jan 2;353(9146):3. PMID: 10023938
CIN - Lancet. 1999 Feb 27;353(9154):753. PMID: 10073541
CIN - Lancet. 1999 Apr 10;353(9160):1276. PMID: 10217116
MH  - Alleles
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Ataxia Telangiectasia/complications/*genetics
MH  - Blotting, Western
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Cyclophosphamide/therapeutic use
MH  - DNA Fingerprinting
MH  - DNA Restriction Enzymes/genetics
MH  - Doxorubicin/therapeutic use
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Heterozygote
MH  - Humans
MH  - Leukemia, B-Cell/complications/drug therapy/*genetics
MH  - Male
MH  - *Mutation
MH  - Prednisolone/therapeutic use
MH  - Tandem Repeat Sequences
MH  - Vincristine/therapeutic use
EDAT- 1999/02/19 00:00
MHDA- 1999/02/19 00:01
CRDT- 1999/02/19 00:00
PHST- 1999/02/19 00:00 [pubmed]
PHST- 1999/02/19 00:01 [medline]
PHST- 1999/02/19 00:00 [entrez]
AID - S0140-6736(98)10117-4 [pii]
AID - 10.1016/S0140-6736(98)10117-4 [doi]
PST - ppublish
SO  - Lancet. 1999 Jan 2;353(9146):26-9. doi: 10.1016/S0140-6736(98)10117-4.