Loss of chromosome arm 18q with tumor progression in head and neck squamous cancer

Abstract

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.

Down-regulated expression of SERPIN genes located on chromosome 18q21 in oral squamous cell carcinomas

“…Region 18q21 is one of the well-known instable chromosome regions in oral carcinomas, at which genetic alterations such as LOH or microsatellite instability have been frequently reported, indicating that there may be unidentified tumor suppressor gene in this region (16,18,20,25). Previously, we found a high frequency of LOH (43.8%) at 18q21 in OSCCs.…”

“…Both SERPINB5 and SERPINB13 genes are located on chromosome 18q, which is the location of the serpin gene cluster and other members of serpin family. Frequent genetic alterations have been observed in this chromosomal region in head and neck malignancies (15)(16)(17)(18)(19)(20). We previously reported that loss of heterozygosity (LOH) at 18q21 was observed in 43.8% of oral squamous cell carcinomas, and that this was significantly correlated with the clinicopathological features (21).…”

Genomic profiles and CRTC1–MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma

“…Heterozygous loss of 18q has been reported in several types of carcinomas, for example colon cancer, 33 pancreatic carcinoma, 34 and head and neck squamous cell carcinoma. 35 These losses, including the tumor suppressor genes SMAD4, DCC, and GALR1, are associated with tumor progression and unfavorable prognosis. 33,34,36 Of interest, all but one of our mucoepidermoid carcinomas with loss of 18q were high-grade tumors that developed metastases (five cases) and/or recurrences (three cases).…”

Epigenetic Loss of Mucosa-Associated Lymphoid Tissue 1 Expression in Patients with Oral Carcinomas

“…In oral carcinomas, expression of the tumor suppressors p53, p14 ARF , p16 INK4a , FHIT, and RSSF1 was frequently inactivated in the early stage of carcinogenesis (1). Allelic imbalance at chromosome locus 18q is associated with progression and poor patient survival of head and neck carcinomas (2,3), and genetic abnormalities at 18q21 are observed in carcinomas of the oral cavity (National Center for Biotechnology Information Entrez Cancer Chromosome Database 3 ) and others (4)(5)(6). Although one tumor suppressor gene, deleted in colorectal carcinoma (DCC), exists at 18q21.1, recent investigations suggest the presence of additional tumor suppressors at 18q21.31 (7,8).…”