Loss of chromosome arm 18q with tumor progression in head and neck squamous cancer.
Loss of 18q was analyzed in 21 sets of head and neck squamous cell carcinoma (HNSCC) cell lines derived from primary and secondary tumors in the same patients. Only 3 of the 21 cell line pairs had no loss of 18q. In the remaining 18 sets, loss of heterozygosity (LOH) affecting 18q was found in either the primary or the secondary lines or both. In every case but one, the same chromosome was affected in both the primary and secondary cell lines. In 8 sets, the 18q loss occurred in the primary tumor and remained stable through the subsequent tumor progression. The primary and secondary lines differed in 18q loss in 10 of 18 (56%) cases with 18q LOH. In 3 of the 10 pairs that differed, 18q LOH was found in only the primary line, indicating that the loss developed after the metastatic or recurrent tumor population had diverged from the primary tumor population. In the other 7 pairs, 18q LOH developed or progressed with tumor recurrence or metastasis. Of these, 3 of 7 had 18q LOH in only the secondary lines, and 4 of 7 had 18q LOH in both the primary and secondary lines, but the extent of LOH was greater in the secondary lines than in the primary lines, indicating that additional rearrangements of the same chromosome occurred with progression. These cases showed that interstitial loss often progresses to consolidated loss in vivo. However, in vitro, the cell lines from the primary tumors with interstitial loss maintain those chromosomes over long-term culture. LOH on 18q in cell lines from previously untreated primary tumors was significantly associated with advanced tumor stage (P=0.0242) and decreased survival (P=0.0453). The findings are consistent with the concept that 18q LOH is an event associated with tumor progression and suggest that inactivation and loss of one or more genes on 18q contributes to aggressive tumor behavior.
Department of Otolaryngology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Satoru
S
Takebayashi
Arthur
A
Hickson
Tetsuya
T
Ogawa
Kwang-Yoon
KY
Jung
Hiroyuki
H
Mineta
Yo
Y
Ueda
Reidar
R
Grénman
Susan G
SG
Fisher
Thomas E
TE
Carey
D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction
D005819:Genetic Markers