Genome-Wide Analyses on Loss of Heterozygosity in Head and Neck Squamous Cell Carcinomas

Beder, Levent Bekir; Gündüz, Mehmet; Ouchida, Mamoru; Fukushima, Kunihiro; Gündüz, Esra; Ito, Sachio; Sakai, Akiko; Nagai, Noriyuki; Nishizaki, Kazunori; Shimizu, Kenji

doi:10.1097/01.lab.0000047489.26246.e1

Cited by 79 publications

(57 citation statements)

References 44 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These alterations are preferentially associated with tumor progression. To date, in oral cancer including oral squamous cell carcinoma (OSCC), loss of heterozygosity (LOH) has been identified on chromosomes 3p, 9p, 13q, 15q and 17p (Beder et al, 2003). These findings suggest that some of these regions may contain a tumor suppressor gene.…”

Section: Introductionmentioning

confidence: 95%

Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array

Nakaya

Arita

et al. 2007

Oncogene

View full text Add to dashboard Cite

Homozygous deletions (HD) provide an important resource for identifying the location of candidate tumor suppressor genes. To identify the tumor suppressor gene in oral cancer, we employed high-resolution comparative genomic hybridization (CGH)-array analysis. We identified a homozygous loss of FAT (4q35), a new member of the human cadherin superfamily, from genome-wide screening of copy number alterations in one primary oral cancer. This result was evaluated by genomic polymerase chain reaction in 13 oral cancer cell lines and 20 primary oral cancers and Southern blot in the cell lines. We found frequent exonic HD of FAT in the cell lines (3/13, 23%) and in primary oral cancers (16/20, 80%). FAT expression was absent in these cell lines. Homozygous deletion hot spots were observed in exon 1 (9/20, 45%) and exon 4 (7/20, 35%). Moreover, loss of gene expression was identified in other types of squamous cell carcinoma. The methylation status of the FAT CpG island in squamous cell carcinomas correlated negatively with its expression. Our results identify mutations in FAT as an important factor in the development of oral cancer and indicate the importance of FATs function in some squamous cell carcinomas.

show abstract

Section: Introductionmentioning

confidence: 95%

Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array

Nakaya

Arita

et al. 2007

Oncogene

View full text Add to dashboard Cite

show abstract

“…HNSCC arises by the accumulation of genetic and epigenetic changes in oncogenes, tumor suppressor genes, and/or DNA stability genes (Vogelstein and Kinzler, 2004). Using cytogenetics, loss of heterozygosity (LOH) analysis, and comparative genomic hybridization (CGH), over 20 recurrent chromosomal alterations have been found in invasive HNSCCs, including losses at 3p, 9p, and 17p, and gains at 3q26 and 11q13 (Bockmuhl et al, 2000;Gollin, 2001;Beder et al, 2003;Tsao et al, 2004;Wreesmann et al, 2004). The relatively high frequency of these chromosomal aberrations, which occur usually in over 30% of carcinomas, or the association with prognosis argues for a role in head and neck carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus

et al. 2005

View full text Add to dashboard Cite

Oncogene-expressing human papillomavirus type 16 (HPV16) is found in a subset of head and neck squamous cell carcinomas (HNSCC). HPV16 drives carcinogenesis by inactivating p53 and pRb with the viral oncoproteins E6 and E7, paralleled by a low level of mutations in TP53 and allelic loss at 3p, 9p, and 17p, genetic changes frequently found in HNSCCs of nonviral etiology. We hypothesize that two pathways to HNSCC exist: one determined by HPV16 and the other by environmental carcinogens. To define the critical genetic events in these two pathways, we now present a detailed genome analysis of HNSCC with and without HPV16 involvement by employing high-resolution microarray comparative genomic hybridization. Four regions showed alterations in HPV-negative tumors that were absent in HPV-positive tumors: losses at 3p11.2-26.3, 5q11.2-35.2, and 9p21.1-24, and gains/amplifications at 11q12.1-13.4. Also, HPV16-negative tumors demonstrated loss at 18q12.1-23, in contrast to gain in HPV16-positive tumors. Seven regions were altered at high frequency (>33%) in both groups: gains at 3q22.2-qter, 5p15.2-pter, 8p11.2-qter, 9q22-34.1, and 20p-20q, and losses at 11q14.1-qter and 13q11-33. These data show that HNSCC arising by environmental carcinogens are characterized by genetic alterations that differ from those observed in HPV16-induced HNSCC, and most likely occur early in carcinogenesis. A number of genetic changes are shared in both tumor groups and can be considered crucial in the later stages of HNSCC progression.

show abstract

“…The overall 5-year survival rate of patients with this cancer is comparatively low, especially because 20-30% of these patients develop other tumors in the upper aerodigestive tract 3 and due to the high incidence of recurrent disease at the primary site or in the regional lymph nodes. 4 In the last years, many efforts had been made to determine the mechanisms involved in the development of head and neck squamous cell carcinoma. In addition to external risk factors like nicotine and alcohol abuse 5 or an infection with human papillomavirus (HPV), 6 a multistep process of accumulated genetic and epigenetic alterations probably accounts for head and neck carcinoma as for most of the sporadic solid tumors.…”

mentioning

confidence: 99%

Loss of heterozygosity at 15q21.3 correlates with occurrence of metastases in head and neck cancer

Poetsch

Kleist

2006

Modern Pathology

View full text Add to dashboard Cite

Deletions on the long arm of chromosome 15 suggesting the presence of potential tumor suppressor genes have been found in several tumors including carcinomas of the colorectum, urinary bladder, breast, lung, and head and neck. Here, we analyzed allelic imbalance on chromosome 15q in head and neck carcinomas and corresponding lymph node metastases to define common regions of aberrations with potential involvement in development and progression of these tumors. We studied a panel of 40 polymorphic microsatellite markers, spanning 15q13-15q26, in 63 head and neck carcinomas and 38 lymph node metastases. Loss of heterozygosity (LOH) could be demonstrated in 34 primary tumors (54%) and 35 metastases (92%). Aberration mapping defined three minimum regions of aberrations: a region between the markers D15S106 and D15S1029 in 15q21.3 (estimated as 3.9 Mb; region 1) was affected in the majority of tumors, whereas two other regions between D15S144 and D15S1040 in 15q13.3-14 (estimated as 2.4 Mb; region 2) and between D15S130 and D15S985 in 15q26.2-26.3 (estimated as 4.7 Mb; region 3) were less often involved. Allelic loss in region 1 correlated with T stages (P ¼ 0.0029) and metastatic potential (P ¼ 0.0018). LOH in regions 2 and 3 occurred predominantly in metastases (P ¼ 0.0129 and P ¼ 0.0013, respectively). No correlation with grading, localization, or clinical outcome could be established for any of the affected regions. Our data hint at aberrations in 15q21.3 as a possible important characteristic for head and neck squamous cell carcinomas with risk of progression.

show abstract

Genome-Wide Analyses on Loss of Heterozygosity in Head and Neck Squamous Cell Carcinomas

Cited by 79 publications

References 44 publications

Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array

Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array

Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus

Loss of heterozygosity at 15q21.3 correlates with occurrence of metastases in head and neck cancer

Contact Info

Product

Resources

About