A deletion linked to a poly(ADP-ribose) polymerase gene on chromosome 13q33-qter occurs frequently in the normal black population as well as in multiple tumor DNA.
The nuclear enzyme poly(ADP-ribose) polymerase (PADPRP) is thought to play a role in DNA recombination, replication, and repair. In view of the implication of these processes in tumorigenesis, and based on preliminary evidence which indicated the presence of an extraneous polymorphic restriction fragment for murine PADPRP loci in strains of mice susceptible to plasmacytomas, we investigated correlations between the restriction fragment length polymorphism of the PADPRP gene(s) and human Burkitt lymphoma. No increase in the frequency of polymorphisms on chromosome 1 (containing the active gene) or on chromosome 14 (a pseudogene) was observed. However, restriction fragment length polymorphism analysis of PADPRP sequences on chromosome 13 (either a processed pseudogene or a gene with extensive identity to PADPRP) revealed that of 19 DNA samples derived from endemic Burkitt lymphoma all contained at least one copy of a rare allele (B). Simple two-allele (A/B) polymorphisms in this PADPRP-like locus were identified by digestion with a number of restriction enzymes including HindIII, PstI, KpnI, and MspI. These restriction fragment length polymorphisms always segregated together, suggesting that they identify a deletion within or close to the PADPRP sequences on chromosome 13, which we mapped precisely to 13q33-qter. Based upon family studies the A and B alleles were shown to be transferred in a Mendelian codominant fashion. Subsequently, this probe was used as a linkage marker to study the frequency of this deletion in various tumors including B-cell follicular lymphomas, small cell lung carcinomas, breast carcinomas, and colorectal carcinomas. In noncancer control populations, the frequency of this deletion was 3-fold higher among Blacks as compared to Caucasians. When DNA from various tumors was compared to normal DNA from racially appropriate noncancer controls, the frequency of this deletion was still 2- to 3-fold higher in the tumor DNA. Matched samples provided instances of tumor-specific loss of heterozygosity but also revealed that the predominant source of this deletion is the germ line, suggesting that the chromosome 13 region neighboring the PADPRP locus may harbor a gene whose loss may predispose individuals to malignancy.
Bhatia
K G
KG
Department of Biochemistry, Georgetown University School of Medicine, Washington, DC 20007.
Cherney
B W
BW
Huppi
K
K
Magrath
I T
IT
Cossman
J
J
Sausville
E
E
Barriga
F
F
Johnson
B
B
Gause
B
B
Bonney
G
G
D000483:Alleles; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics*; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004273:DNA, Neoplasm / Q000235:genetics* / Q000302:isolation & purification; D005260:Female; D005787:Gene Frequency; D005796:Genes; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D012016:Reference Values; D015183:Restriction Mapping; D014481:United States; D044465:White People / Q000235:genetics; D001741:Black or African American
D004273:DNA, Neoplasm; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases