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[Cancer Research 53, 1498-1502, April 1, 1993]
© 1993 American Association for Cancer Research

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A Homozygous Deletion within the Carbonic Anhydrase-like Domain of the Ptprg Gene in Murine L-Cells1

Kishore K. Wary, Zhuangwei Lou, Arthur M. Buchberg, Linda D. Siracusa, Teresa Druck, Sal LaForgia and Kay Huebner2

Jefferson Cancer Institute, Thomas Jefferson Medical College, Philadelphia, Pennsylvania 19107

Protein tyrosine phosphatases, on purely theoretical grounds, were suggested as possible tumor suppressor genes, and receptor protein tyrosine phosphatase {gamma} (PTPRG) has been proposed, on the basis of its location at human chromosome region 3p14.2, specifically as a tumor suppressor gene for renal cell carcinoma.

We have isolated murine genomic and complementary DNA clones for analysis and mapping of the murine Ptprg locus; interspecific backcross analysis showed that the Ptprg locus maps to the centromeric region of mouse chromosome 14. We also observed a homozygous, intragenic deletion in the Ptprg gene in all clonal derivatives of the original L-cell strain, a methylcholanthrene-treated mouse connective tissue cell line which produces sarcomas in syngeneic mice. The deletion begins in the second intron of the carbonic anhydrase-like domain of the Ptprg gene and ends in the fourth intron of the carbonic anhydrase-like domain. At the genomic level, perhaps several hundred kilobases of DNA are deleted; at the complementary DNA level the 400 base pairs comprising exons 2, 3, and 4 of the carbonic anhydrase-like domain are deleted. By reverse transcription polymerase chain reaction, an amplified fragment is produced from L-cell mRNA which is 400 base pairs shorter than the wild type gene product, suggesting that the deleted gene is transcribed and may produce a protein product.

Thus, mouse L-cells have lost one Ptprg allele and sustained an intragenic deletion in the other; such allele loss and mutation frequently occur at tumor suppressor gene loci.

1 This work was supported by USPHS Grant CA 21124 and by an American Cancer Society Junior Faculty Research Award (L. D. S.).

2 To whom requests for reprints should be addressed, at Jefferson Cancer Institute, Thomas Jefferson Medical College, BLSB, Rm. 1008A, 233 S. 10th St., Philadelphia, PA 19107.

Received 2/ 8/93. Accepted 2/26/93.




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Copyright © 1993 by the American Association for Cancer Research.