title: ATM mutations in B-cell chronic lymphocytic leukemia.
abstract: Mutations in the ATM gene located on the long arm of chromosome 11 at 11q22-23 cause ataxia-telangiectasia, an autosomal recessive disorder that is associated with increased incidence of malignancy and, particularly, lymphoid tumors. A role for ATM in the development of sporadic T-cell chronic leukemias is supported by the finding of loss of heterozygosity at 11q22-23 and ATM mutations in leukemias carrying TCL-1 rearrangements. Approximately 14% of B-cell chronic lymphocytic leukemia (B-CLL), the most common adult leukemia, carry deletions of the long arm of chromosome 11 at 11q22-23. Loss of heterozygosity at 11q22-23 and, more recently, absence of ATM protein, have been associated with poor prognosis in B-CLL. To determine whether the ATM gene is altered in B-CLL, we have sequenced individual ATM exons in six B-CLL cases. We show that the ATM gene is mutated in a fraction of B-CLLs and that mutations can be present in the germ line of patients, suggesting that ATM heterozygotes may be predisposed to B-CLL.
authors.affiliation: Kimmel Cancer Institute and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: F
authors.initials: F
authors.lastname: Bullrich
authors.forename: D
authors.initials: D
authors.lastname: Rasio
authors.forename: S
authors.initials: S
authors.lastname: Kitada
authors.forename: P
authors.initials: P
authors.lastname: Starostik
authors.forename: T
authors.initials: T
authors.lastname: Kipps
authors.forename: M
authors.initials: M
authors.lastname: Keating
authors.forename: M
authors.initials: M
authors.lastname: Albitar
authors.forename: J C
authors.initials: JC
authors.lastname: Reed
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002880:Chromosomes, Human, Pair 11; D004268:DNA-Binding Proteins; D005091:Exons / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases