11p deletions and breakpoints in squamous cell carcinoma: association with altered reactivity with the UM-E7 antibody.
The UM-E7 monoclonal antibody raised against the UM-SCC-I human squamous cell carcinoma (SCC) cell line identifies a cell surface antigen that is strongly expressed in normal tissues. The locus (MICI) controlling the expression of E7 and related cell surface antigens has been mapped to chromosome band 11p13. This band has been identified as a region of cancer-associated aberrations and as the probable locus of a tumor suppressor gene. Although E7 antigen expression is strong in normal keratinocytes, it varies among squamous carcinoma cell lines. Some SCC lines (12/26) exhibit weak expression of the E7 antigen, whereas other SCC cell lines (14/26) and 21 cell lines from other tumor types express the antigen strongly. On the basis of these observations and of mapping data, we postulated that low E7 antigen expression in a subset of SCC cell lines might be associated with chromosomal rearrangement or deletion involving the E7 locus on 11p. Fully evaluable karyotypes were prepared from 19 SCC cell lines, including 11 with weak and eight with strong E7 expression. Eight of the 11 lines with weak E7 expression had 11p abnormalities. Four of these contained 11p deletions, and four others had a breakpoint in 11p. In contrast, none of the cell lines in the group with strong E7 expression had an 11p deletion, although one had a rearrangement with an 11p breakpoint. In the four tumors with visible 11p deletions, the smallest region of overlap corresponded to the 11p13-p14 region. The mean log10 50% endpoint E7 titer in the group with 11p deletions or breakpoints was nearly two orders of magnitude lower than that of the lines with no 11p abnormality (1.95 +/- 0.53) (P less than 0.02). Our results indicate that the UM-E7 antibody identifies tumors with 11p13-p14 deletions and other 11p rearrangements and that the 11p region is a site of nonrandom chromosome rearrangement in a subset of human squamous cancers. The strong association of loss of antigen expression with visible 11p deletion or rearrangement in some tumors suggests that other tumors with this phenotype may contain submicroscopic lesions of 11p13-p14.
Bradford
C R
CR
Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor.
Kimmel
K A
KA
Van Dyke
D L
DL
Worsham
M J
MJ
Tilley
B J
BJ
Burk
D
D
del Rosario
F
F
Lutz
S
S
Tooley
R
R
Hayashida
D J
DJ
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure*; D015321:Gene Rearrangement; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D007621:Karyotyping; D009369:Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D007075:Immunoglobulin M