Identification of new minimally lost regions on 18q in head and neck squamous cell carcinoma

Loss of heterozygosity (LOH) on 18q predicts poor survival in head and neck squamous cell carcinomas (HNSCCs). Several putative tumor suppressor genes , such as DCC, DPFC4/Smad4, and MADR2/Smad2, are mapped to 18q, but thus fa r, the important gene locus in HNSCC is not known. To identify possible gen e loci on 18q, we performed LOH studies using tumor DNA from 57 HNSCC prima ry tumor cell lines and DNA isolated from fibroblasts or lymphoblastoid cel ls from the same patients, Forty-two highly polymorphic microsatellite mark ers spaced not more than 5 chi apart (mean distance, 1.82 cM) spanning the region From D18S44 in 18q11.1 to D18S1141 in 18q23 were used. D18S71 in 18p 11.21 on 18p was also used to dc determine whether the short arm was retain ed. Forty-three of 57 (75%) HNSCC lines showed LOH or isolated allelic imba lance (AI) fur at least one locus on 18q. Although many of the cell lines h ad large distal 18q deletions with a breakpoint between 18q11.1 and 18q12.2 to qter, three loci were identified that were lost in 70% or more of the c ases. The minimally lost regions (MLRs) range in size from 1.5-15.79 chi, T he most proximal is centered on D18S39 (1.56 cM) in band 18q21.1, with LOH or isolated Al in 28 of 38 (74%) of informative cases, The largest (15.8 cM ) begins at D18S61 (28 of 40; 70%) in band 18q22.2 and extends through D18S 50 in 18q23, The third is centered on D18S70 (30 of 10; 75%) in band 18q23 (3.67 chi). OF these MLRs, only the one centered on D18S39 has been implica ted previously in HNSCC, D18S70, the most frequently lost marker, was the o nly marker consistently lost in three tumor cell lines with very minimal lo sses, Um-SCC-19, UM-SCC-67, and UM-SCC-73A. In addition, UM-SCC-91 exhibite d AI only at this locus, and UT-SCC-4 had Al at D18S70 and D18S39 only. Clo se physical mapping of these three regions may pinpoint one or more previou sly unidentified tumor suppressor genes.