Deletion of genetic material from a poly(ADP-ribose) polymerase-like gene on chromosome 13 occurs frequently in patients with monoclonal gammopathies.
Recently, by using a probe for the nuclear DNA repair enzyme poly(ADP-ribose) polymerase gene, a pseudogene was found on the long arm of chromosome 13. RFLP analysis demonstrates the presence of a common "A" allele and a rare "B" allele, which has a deletion of approximately 200 bp. This deletion occurs more frequently in blacks than in whites in the United States. In two B-cell malignancies, Burkitt's and follicular lymphomas, there is a marked increased frequency of the expression of the B allele. Thus, we have analyzed the frequency of this allele in another B-cell malignancy, multiple myeloma (MM), which is also more frequently observed in blacks. We studied 97 patients with MM (41 black and 56 white patients) and 30 patients with the related disorder monoclonal gammopathy of undetermined significance (MGUS; 13 black and 17 white patients). The results demonstrate that the overall frequency of B allele expression (37%) is higher than in a noncancer control population (23%; P < 0.01). This difference is mainly due to the much higher frequency of B expression in black patients (52 versus 35% in black controls; P < 0.01), whereas there is no significant difference in white patients (18 versus 14% in white controls). Overall, B allelic frequency is similar in patients with MM and MGUS. Matched germline and tumor DNA show identical patterns of expression of these alleles. These results suggest germline B allelic expression predisposes one to MM and MGUS.
Cao
J
J
Division of Hematology/Oncology, Department of Veterans Affairs, West Los Angeles, California 90073, USA.
Hong
C H
CH
Rosen
L
L
Vescio
R A
RA
Smulson
M
M
Lichtenstein
A K
AK
Berenson
J R
JR
D000483:Alleles; D044383:Black People / Q000235:genetics*; D015139:Blotting, Southern; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D018076:DNA, Complementary / Q000032:analysis; D006801:Humans; D010265:Paraproteinemias / Q000208:ethnology / Q000235:genetics*; D011064:Poly Adenosine Diphosphate Ribose / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011506:Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics*
D018076:DNA, Complementary; D011506:Proteins; C024857:poly(ADP)-ribosylated proteins; D011064:Poly Adenosine Diphosphate Ribose