title: Acquired chromosome 11q deletion involving the ataxia teleangiectasia locus in B-cell non-Hodgkin's lymphoma: correlation with clinicobiologic features.
abstract: OBJECTIVE
  To study the clinicobiologic significance of acquired 11q deletions involving the ataxia teleangiectasia locus (ATM+/-) in B-cell non-Hodgkin's lymphomas (NHL).
  
  
  METHODS
  Fifty-three indolent lymphomas and 82 aggressive lymphomas were studied by conventional cytogenetic analysis and by fluorescence in situ hybridization using an 11q22-23 probe recognizing ATM sequences. Pertinent clinical data were collected.
  
  
  RESULTS
  A hemizygous ATM deletion was seen in 44% to 88% of the interphase cells in 15 cases (11.1%); four patients had an indolent lymphoma (follicular center cell lymphoma), and 11 patients had an aggressive lymphoma (five mantle-cell lymphomas [MCLs] and six diffuse large-cell lymphomas). Dual-color hybridization studies showed ATM deletion to be possibly a secondary aberration in three patients with MCL. Ten out of 15 ATM+/- patients had a complex karyotype, 11 out of 15 had more than 90% abnormal metaphases (AA karyotype status), and +12, 13q14 deletion, and 17p13 deletion were seen in seven, four, and five cases, respectively. Patients with ATM+/- more frequently had a complex karyotype (P =.01) and the AA karyotype (P =.04) compared with patients without ATM+/-. With the exception of a poor performance status (P =.001), no correlation was found between ATM+/-, initial clinical variables, and complete remission rate; whereas a highly significant association was found with shorter survival (P <.0001). This cytogenetic lesion maintained its prognostic importance in multivariate analysis (P =.0004), along with performance status (P =.0006), serum lactate dehydrogenase level (P =.03), splenomegaly (P =.01), and histologic grade (P =.03). When analyzing indolent lymphomas and aggressive lymphomas separately, ATM+/- maintained its prognostic importance as an independent variable in both histologic groups (P =.0001 and P =.016, respectively).
  
  
  CONCLUSIONS
  Though possibly not representing a primary genetic lesion in the majority of cases, the acquired ATM+/- status has clinicobiologic importance in NHL, possibly representing a major cytogenetic determinant of outcome.
authors.affiliation: Dipartimento di Scienze Biomediche e Terapie Avanzate, Sezione di Ematologia, Sezione di Microbiologia, University of Ferrara, Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cuneo
authors.forename: R
authors.initials: R
authors.lastname: Bigoni
authors.forename: G M
authors.initials: GM
authors.lastname: Rigolin
authors.forename: M G
authors.initials: MG
authors.lastname: Roberti
authors.forename: R
authors.initials: R
authors.lastname: Milani
authors.forename: A
authors.initials: A
authors.lastname: Bardi
authors.forename: C
authors.initials: C
authors.lastname: Minotto
authors.forename: P
authors.initials: P
authors.lastname: Agostini
authors.forename: C
authors.initials: C
authors.lastname: De Angeli
authors.forename: M G
authors.initials: MG
authors.lastname: Narducci
authors.forename: S
authors.initials: S
authors.lastname: Sabbioni
authors.forename: G
authors.initials: G
authors.lastname: Russo
authors.forename: M
authors.initials: M
authors.lastname: Negrini
authors.forename: G
authors.initials: G
authors.lastname: Castoldi
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D007621:Karyotyping; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015996:Survival Rate; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases