Expression of the DMBT1 gene is frequently suppressed in human lung cancer

DMBT1 (deleted in malignant brain tumors) is a candidate tumor suppressor g ene that has been mapped to chromosome 10q25.3-q26.1, a region in which fre quent loss of heterozygosity (LOH) has been observed in several human tumor s. Since DMBT1 is highly expressed in the lung, we analyzed LOH at the DMBT 1 locus and expression of this gene in lung cancer. Thirty-five (53%) of 66 primary lung cancers showed LOH, and diminished expression of DMBT1 was ob served in 20 (91%) of 22 lung cancer cell lines: three (14%) of them showed loss of expression. We further determined the primary structure of DMBT1 a nd analyzed genetic alterations in this gene using 23 lung cancer cell line s. Two (9%) of them had homozygous deletion within the gene, and two cell l ines had genetic aberrations: one was a rearrangement involving exons 5 and 6, and the other was a missense mutation at codon 52. These results sugges t that inactivation of the DMBT1 gene plays an important role in human lung carcinogenesis.