Somatic mutation and homozygous deletion of PTEN/MMAC1 gene at 10q23 in renal cell carcinoma

We studied chromosome 10q loss of heterozygosity and PTEN/MMAC1 gene inacti vation in renal cell carcinoma (RCC). Fifty-four cases of RCCs were analyse d by three 10q RFLP markers. Forty one of them were heterozygous for at lea st one of the markers, of which fourteen showed LOH (34%). Six tumors which showed 10q deletion for RFLP markers and six randomly selected tumors with out RFLP LOH were included in an extended study of 10q by eight microsatell ite markers. Eight of these cases showed LOH with two smallest deleted regi ons (SRO) at 10q23 delineated by markers D10S541 and D10S579 while the othe r distal SRO is between markers D10S587 and D10S212 at 10q25-26. The five t umors with LOH covering 10q23 were selected for mutation analysis of PTEN/M MAC1 genes. One tumor without LOH of 10q23 was selected as a control. Using direct sequencing of nine exons, we found three different base pair change s in three tumors wit LOH. Nine RCC cell lines were analysed for PTEN/MMAC1 gene inactivation. One homozygous deletion was detected in the cell line U OK147. No expression of PTEN/MMAC 1 gene was detect by RT-PCR in the cell l ine UOK147.