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The FHIT and PTPRG Genes Are Deleted in Benign Proliferative Breast Disease Associated with Familial Breast Cancer and Cytogenetic Rearrangements of Chromosome Band 3p14¹

Departments of Clinical Genetics [I. P., N. P., S. T., C. P., F. Me., U. K., F. Mi., P. Å.] and Oncology [Å. B.], Lund University Hospital, 221 85 Lund, Sweden, and Department of Genetics, Papanikolaou Research Center, Saint Savas Hospital, 115 22 Athens, Greece [N. P.]

We have used nested reverse transcription-PCR (RT-PCR) and PCR on genomic DNA to search for aberrations in the FHIT and PTPRG genes, both located in chromosomal band 3p14.2, in specimens from cytogenetically analyzed benign breast lesions (three samples with atypical hyperplasia and one with fibroadenosis) from two women belonging to breast cancer families. The transcription analysis showed that the FHIT gene was either not expressed or that its expression was dramatically reduced to a level not detectable by nested RT-PCR in the samples with atypical hyperplasia. Genomic analysis of exons 3 and 5 of FHIT and exon 12 of PTPRG provided evidence that these DNA segments were homozygously deleted in the majority of the cells. These data are in line with the histopathological features and cytogenetic findings in the three samples; none contained normal parenchyma, and all had chromosomal aberrations involving band 3p14. RT-PCR analysis of the fibroadenosis specimen, which had a normal karyotype, detected the expected 856-bp fragment as well as an additional alternative transcript variant of FHIT with 1014 bp. The additional 158-bp sequence, which may add 38 amino acids to the NH₂-terminal part of the previously described FHIT protein, was inserted between exons 4 and 5 and seems to be a new exon located in intron 4 of FHIT.

¹ Supported by grants from the Swedish Cancer Society and the Medical Faculty of Lund University.

² To whom requests for reprints should be addressed, at Department of Clinical Genetics, Lund University Hospital, S-221 85 Lund, Sweden. Phone: 46-46-173739; Fax: 46-46-131061.

Received 7/19/96. Accepted 9/17/96.

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