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Blood, Vol. 95 No. 5 (March 1), 2000:
pp. 1869-1871
BRIEF REPORT
Germline CDKN2A mutation implicated in predisposition to
multiple myeloma
David Dilworth,
Ling Liu,
A. Keith Stewart,
James R. Berenson,
Norman Lassam, and
David Hogg
From the Departments of Medical Biophysics, Clinical Science, and
Medicine, University of Toronto, Toronto, Ontario, Canada, and
the Department of Medical Oncology, University of
California at Los Angeles, Los Angeles, CA.
Germline mutations of the CDKN2A
(p16INK4A) tumor suppressor gene predispose
patients to melanoma and pancreatic carcinoma. In contrast, mutations
of the murine CDKN2A gene predispose BALB/c mice to
pristane-induced plasmacytoma. We describe here a family in which a
germline mutation of CDKN2A is present in 4 individuals who
developed melanoma as well as in a fifth family member who is suffering
from multiple myeloma. To determine whether the CDKN2A mutation
predisposed the myeloma patient to her disease, we carried out loss of
heterozygosity studies on sorted bone marrow from this individual and
observed loss of the wild type CDKN2A allele in the malignant
plasma cells. We suggest that germline mutations of CDKN2A may
predispose individuals to a wider variety of malignancy than has been
hitherto reported, but that the expression of these cancers may depend
heavily on the genetic background of the patient.
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