ARHI is the center of allelic deletion on chromosome 1p31 ovarian and breast cancers

In our previous work, we had characterized ARHI as an imprinted putative tu mor-suppressor gene in ovarian and breast cancers. ARHI is expressed in pri mary breast and ovarian cell lines but largely absent from the correspondin g malignant tumors, Moreover, the non-imprinted functional allele is typica lly deleted in malignant cells. Since ARHI had been mapped to 1p31, a commo n deletion site in breast and ovarian cancer and male germ-cell tumors, in this study, we see out: to define precisely the physical location of ARHI a t 1p31 and to determine if this location lies within the smallest common re gion of deletion in breast and ovarian cancers. To this end, we first carri ed out radiation hybrid mapping of ARHI and surrounding markers, followed b y a high-resolution study of loss of heterozygosity at 1p31 in 49 ovarian a nd breast cancers. Combining a radiation hybrid map and a physical map of t he region encompassing ARHI, 3 discrete regions of minimal deletion were fo und at 1p31 in breast and ovarian cancers. ARHI is the most common deletion region at 1p31. Two other less common regions of deletion were found centr omeric to this gene. One of them centered on D15207 and the other one inclu ded and was proximal to D1S488, We also confirmed the preferential loss of non-imprinted functional allele in 7 of 9 tumor specimens, These data suppo rt the possibility that ARHI is a tumor-suppressor gene and suggest: that a dditional tumor-suppressor genes may lie proximal to ARHI at 1p31, The data obtained from our study should aid in the identification and characterizat ion of genes in this novel imprinted region, (C) 2000 Wiley-Liss, Inc.