OBJECTIVES: We sought to assess loss of heterozygosity (LOH) profiles of 3p, 6q, 8q, 10q, 12q, 13q, and 17p and to identify the tumor suppressor genes involved in salivary gland neoplasms.
STUDY DESIGN: LOH analysis was performed using 26 microsatellite markers by polymerase chain reaction—polyacrylamide gel electrophoresis method in 20 benign and 6 malignant salivary gland tumors.
RESULTS: Overall, LOH was detected in at least one informative locus in 18 of 20 (90%) of benign tumors and in all of 6 cases of malignant tumors. High LOH frequencies were revealed at the loci D3S1307 (22%, 3p26), D3S966 (41%, 3p21), D6S255 (27%, 6q25), D8S166 (25%, 8q12), D8S199 (21%, 8q24), and D10S1765 (28%, 10q23) in benign tumors, defining the hotspot regions for putative tumor suppressor genes.
CONCLUSIONS AND SIGNIFICANCE: The hotspot regions defined by the present study suggest that new tumor suppressor genes related to the development of salivary gland tumors may reside at several chromosomal loci, including loci at 3p, 6q, 8q and 10q.
Get full access to this article
View all access options for this article.
References
1.
BederLBGunduzMOuchidaM, et al. Genome-wide analyses on loss of heterozygosity in head and neck squamous cell carcinomas. Lab Invest2003;83:99–105.
2.
El-NaggarAKCallenderDCoombesMM, et al. Molecular genetic alterations in carcinoma ex-pleomorphic adenoma: a putative progression model?Genes Chromosomes Cancer2000;27:162–8.
3.
El-NaggarAKHurrKKaganJ, et al. Genotypic alterations in benign and malignant salivary gland tumors: histogenetic and clinical implications. Am J Surg Pathol1997;21:691–7.
4.
GillenwaterAHurrKWolfP, et al. Microsatellite alterations at chromosome 8q loci in pleomorphic adenoma. Otolaryngol Head Neck Surg1997;117:448–52.
5.
JohnsMMWestraWHCalifanoJA, et al. Allelotype of salivary gland tumors. Cancer Res1996;56:1151–4.
6.
RutherfordSHamptonGMFriersonHF, et al. Mapping of candidate tumor suppressor genes on chromosome 12 in adenoid cystic carcinoma. Lab Invest2005;85:1076–85.
7.
SahlinPMarkJStenmanG.Submicroscopic deletions of 3p sequences in pleomorphic adenomas with t(3;8)(p21;q12). Genes Chromosomes Cancer1994;10:256–61.
8.
GunduzMOuchidaMFukushimaK, et al. Genomic structure of the human ING1 gene and tumor-specific mutations detected in head and neck squamous cell carcinomas. Cancer Res2000;60:3143–6.
9.
KissHKedraDYangY, et al. A novel gene containing LIM domains (LIMDI) is located within the common eliminated region 1 (C3CER1) in 3p21.3. Hum Genet1999; 105: 552–9.
10.
ShriverSPShriverMDTirpakDL, et al. Trinucleotide repeat length variation in the human ribosomal protein L14 gene (RPL14): localization to 3p21.3 and loss of heterozygosity in lung and oral cancers. Mutat Res1998; 406: 9–23.
11.
HuangXPZhaoCXLiQJ, et al. Alteration of RPL14 in squamous cell carcinomas and preneoplastic lesions of the esophagus. Gene2006;366:161–8.
12.
ChanoTKontaniKTeramotoK, et al. Truncating mutations of RB1CC1 in human breast cancer. Nat Genet2002;31:285–8.
13.
JandrigBSeitzSHinzmannB, et al. ST18 is a breast cancer tumor suppressor gene at human chromosome 8q11.2. Oncogene2004; 23: 9295–302.
14.
KishiMNakamuraMNishimineM, et al. Loss of heterozygosity on chromosome 6q correlates with decreased thrombospondin-2 expression in human salivary gland carcinomas. Cancer Sci2003;94:530–5.
15.
AbdollahiAPisarcikDRobertsD, et al. LOT1 (PLAGL1/ZAC1), the candidate tumor suppressor gene at chromosome 6q24-25, is epigenetically regulated in cancer. J Biol Chem2003;278:6041–9.
16.
TakahashiYMiyoshiYTakahataC, et al. Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers. Clin Cancer Res2005;11:1380–5.
17.
RutherfordSYuYRumpelCA, et al. Chromosome 6 deletion and candidate tumor suppressor genes in adenoid cystic carcinoma. Cancer Lett2006;236:309–17.
18.
EnlundFPerssonFStenmanG.Molecular analyses of the candidate tumor suppressor gene, PLAGL1, in benign and malignant salivary gland tumors. Eur J Oral Sci2004;112:545–7.
19.
SoodRMakalowskaIGaldzickiM, et al. Cloning and characterization of a novel gene, SHPRH, encoding a conserved putative protein with SNF2/helicase and PHD-finger domains from the 6q24 region. Genomics2003;82:153–61.
20.
KishiMNakamuraMNishimineM, et al. Genetic and epigenetic alteration profiles for multiple genes in salivary gland carcinomas. Oral Oncol2005;41:161–9.
21.
FowlerMHFowlerJDucatmanB, et al. Malignant mixed tumors of the salivary gland: a study of loss of heterozygosity in tumor suppressor genes. Mod Pathol2006;19:350–5.
