title: Characterization of familial Waldenstrom's macroglobulinemia.
abstract: BACKGROUND
  Familial clustering of B-cell disorders among Waldenström's macroglobulinemia (WM) patients has been reported, though the frequency and any differences in disease manifestation for familial patients remain to be defined.
  
  
  METHODS
  We therefore analyzed clinicopathological data from 257 consecutive and unrelated WM patients. Forty-eight (18.7%) patients had at least one first-degree relative with either WM (n = 13, 5.1%), or another B-cell disorder including non-Hodgkin's lymphoma (n = 9, 3.5%), myeloma (n = 8, 3.1%), chronic lymphocytic leukemia (n = 7, 2.7%), monoclonal gammopathy of unknown significance (n = 5, 1.9%), acute lymphocytic leukemia (n = 3, 1.2%) and Hodgkin's disease (n = 3, 1.2%). Patients with a familial history of WM or a plasma cell disorder (PCD) were diagnosed at a younger age and with greater bone marrow involvement.
  
  
  RESULTS
  Deletions in 6q represented the only recurrent structural chromosomal abnormality and were found in 13% of patients, all non-familial cases. Interphase FISH analysis demonstrated deletions in 6q21-22.1 in nearly half of patients, irrespective of familial background.
  
  
  CONCLUSIONS
  The above results suggest a high degree of clustering for B-cell disorders among first-degree relatives of patients with WM, along with distinct clinical features at presentation based on familial disease cluster patterns. Genomic studies to delineate genetic predisposition to WM are underway.
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana Farber Cancer Institute, Boston, MA 02115, USA. steven_treon@dfci.harvard.edu
authors.forename: S P
authors.initials: SP
authors.lastname: Treon
authors.forename: Z R
authors.initials: ZR
authors.lastname: Hunter
authors.forename: A
authors.initials: A
authors.lastname: Aggarwal
authors.forename: E P
authors.initials: EP
authors.lastname: Ewen
authors.forename: S
authors.initials: S
authors.lastname: Masota
authors.forename: C
authors.initials: C
authors.lastname: Lee
authors.forename: D Ditzel
authors.initials: DD
authors.lastname: Santos
authors.forename: E
authors.initials: E
authors.lastname: Hatjiharissi
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.forename: X
authors.initials: X
authors.lastname: Leleu
authors.forename: O
authors.initials: O
authors.lastname: Tournilhac
authors.forename: C J
authors.initials: CJ
authors.lastname: Patterson
authors.forename: R
authors.initials: R
authors.lastname: Manning
authors.forename: A R
authors.initials: AR
authors.lastname: Branagan
authors.forename: C C
authors.initials: CC
authors.lastname: Morton
mesh_terms: D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015994:Incidence; D007399:Interphase; D007621:Karyotyping; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology