Identification of two distinct tumor-suppressor loci on the long arm of chromosome 10 in small cell lung cancer

Recent cytogenetic studies indicated that loss of the long arm of chromosome 10 is a frequent event in small cell lung cancer (SCLC) and that a common region of the deletion is at 10q24-qter, which suggests the presence of a tumor-suppressor gene there. To map precise tumor-suppressor loci on the chromosome arm for further positional cloning efforts, we tested 46 primary SCLCs using microsatellite analysis. By analysing 11 highly polymorphic microsatellite markers located in 10q23-q26, we found that at least 78% (36/46) of the tumors exhibited loss of heterozygosity (LOH) at 10q with at least two distinct minimally deleted regions. LOH at one region (10q24) was found in at least 74% (32/43) of informative cases with a minimally deleted region between D10S198 and D10S192 (about 2 cM); LOH at another region (10q24-q25) was observed in at least 66% (29/44) of informative tumors with a minimally deleted region between D10S221 and D10S587 (about 11 cM). LOH at both regions or across both regions was observed in at least 52% (24/46) of the tumors tested. However, no mutations or homozygous deletions were found in the coding region of MXI1, a candidate tumor suppressor gene at 10q24-q25, in a panel of SCLC cell lines. Our data demonstrate that at least two tumor-suppressor loci exist on 10q and that they may play an important role in SCLC tumorigenesis.