Human rgr: transforming activity and alteration in T-cell malignancies.
We have previously identified the oncogene rgr (ralGDS related) in DNA derived from a rabbit squamous cell carcinoma. Here we describe the identification of the human orthologue of the rabbit rgr gene termed hrgr (human ralGDS related). Four alternatively spliced full-length hrgr transcripts were isolated from normal human testes and liver libraries. Truncation of hrgr confers transforming ability to its cDNA. Using a RT-PCR assay we have been able to detect the expression of an abnormally truncated transcript in several human T-cell lymphoma lines, and in fresh tissue samples of patients with T-cell malignancies. In the DHL cell line, an Anaplastic Large Cell Lymphoma (ALCL) line, a DNA rearrangement was detected within the hrgr gene region. We propose that these T-cell lymphomas, at least in part, owe their malignant phenotypes to genetic alterations of the hrgr gene. These findings also raise the possibility that mutations in the hrgr gene are involved in other malignancies.
Department of Pathology, 550 First Ave., New York University Medical Center, New York, NY 10016, USA.
Peter
P
Leonardi
Ezra
E
Kassin
Inmaculada
I
Hernandez-Muñoz
Roberto
R
Diaz
Giorgio
G
Inghirami
Angel
A
Pellicer
D016475:3T3 Cells; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D006801:Humans; D019169:Jurkat Cells; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020161:Physical Chromosome Mapping; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D013737:Testis / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D020726:ral Guanine Nucleotide Exchange Factor / Q000737:chemistry*
D015513:Oncogene Proteins; D012333:RNA, Messenger; D020726:ral Guanine Nucleotide Exchange Factor