Genetic and epigenetic inactivation of LTF gene at 3p21.3 in lung cancers

Allelic loss on the short arm of chromosome 3 is one of the most common events in the pathogenesis of lung cancer. The lactotransferrin gene ( LTF, also referred to as the lactoferrin gene, LF ) is located at 3p21.3 common eliminated region 1, which is frequently deleted in lung and other cancers. The expression of the LTF gene was absent in 16 (59%) of 27 small cell lung cancer cell lines, 33 (77%) of 43 nonsmall‐cell lung cancer (NSCLC) cell lines and 7 (54%) of 13 primary NSCLC, while LTF mRNA was overexpressed in 3 (7%) of 43 NSCLC cell lines. Its expression was restored by treatment with 5‐aza‐2′‐deoxycytidine (5‐aza‐dC), trichostatin A (TSA) or a combination of both in a subset of lung cancer cell lines without LTF expression. In addition, we found 8 different types of nucleotide substitutions and one frameshift mutation. These results indicate that the LTF gene is inactivated by genetic and epigenetic mechanisms in lung cancer. © 2005 Wiley‐Liss, Inc.