Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

Head and Neck: Oral squamous cell carcinoma

Written2006-09Yuesheng Jin , Charlotte Jin
Dept clinical Genetics, University Hospital, SE-221 85 Lund, Sweden

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C030-C031,C039-C041,C048-C052,C058-C062,C068-C069 GUM, FLOOR OF MOUTH, & OTHER MOUTH
ICD-Morpho 8070/3 Squamous cell carcinoma, NOS
Atlas_Id 5368
Phylum Head and Neck:Mouth-Oropharynx:Epithelium:Squamous cell carcinoma
Note An invasive epithelial neoplasm with varying degrees of squamous differentiation that arises from the following anatomic sites: the oral cavity, particularly oral soft tissues including the gingival and alveolar mucosa, floor of the mouth, tongue, soft and hard palates, tonsils and oropharynx. Oral squamous cell carcinomas (SCC) have a propensity to early and extensive lymph node metastases.

Clinics and Pathology

Epidemiology Oral cancer consistently ranks as one of the top ten cancers worldwide, with broad differences in geographic distribution. They represent approximately 5% of cancers in men and 2% in women. Oral SCC often develops after the age of 50, with a highest peak in the sixth decade of life. The major risk factor for these neoplasms is chronic exposure of oral mucosa to tobacco and alcohol. Apart from these, human papilloma virus (HPV) infection, especially HPV 16 and 18, are found in a variable but small proportion of oral, and up to 50% of tonsillar and oropharyngeal SCC. It has been realized for a long time that patients with oral SCC are at risk of second tumors in the upper aerodigestive tract, reported to occur in 10-35% of case.
Clinics More than 90-95% of oral cancers are SCC or one of its variants. SCC typically presents as a persistent mass, nodule, or indurate ulcer. The three most common sites of involvement are tongue, lip and floor of the mouth. They can develop from precancerous lesions, such as leukoplakia and erythroplakia, or apparently normal epithelium. Histopathologically, they can be categorized into three degrees of differentiation:
Well differentiated disease shows greater than 75% keratinization.
Moderately differentiated disease contributes to the bulk of SCC and is characterized by 25% to 75% keratinization.
Poorly differentiated disease demonstrates less than 25% keratinization.
The degree of differentiation may vary from one part of the tumor to another. Tumor stage is according to TNM classification.
Prognosis Histological grade correlates poorly with patient outcome and thus has limited value for prognostication. Tumor size and nodal status are the most significant prognostic factors. At the time of diagnosis, the majority of patients with SCC present advanced disease (stage III-IV), and approximately one third of them show lymph node metastasis. After curative treatment, about 50% of the patients suffer recurrences; 80% within 2 years and the remaining within 4 years. The major cause of death is loco-regional failure.

Cytogenetics

Note Classical cytogenetics
Clonal chromosome abnormalities have been described in about 250 oral SCC (115 of oral cavity, 81 of tongue, and 53 of oro- or hypopharynx). The great majority of these neoplasms are characterized by complex karyotypes with a clearly nonrandom pattern of losses and gains of chromosome segments. This is in line with the notion that oral SCC, like most of other epithelial malignancies, develop by the accumulation of multiple genetic aberrations.
The most frequent imbalances were loss of 3p, 8p, 11q, 15p, 13p, 14p, 4p, 10p, 6q, 2q33-qter, and chromosomes Y, 21, 22, and 18, and gain of chromosomes 20 and 7, 8q and 11q13. The most common structural aberrations were i(8q), homogeneously staining region (hsr), i(3q), i(5p), i(1q), del(16)(q22), i(13q), i(14q), del(2)(q33), and del(3)(p11). Another striking feature is that close to half of all structural rearrangements involve breakpoints in the centromeric or juxtacentromeric bands, particularly in chromosomes 8, 1, 3, 5, 13, 14 and 15.

Molecular consequences of chromosomal aberrations revealed by fluorescence in situ hybridization (FISH)
A number of fluorescence in situ hybridization (FISH), including multicolor FISH, studies have been undertaken in cytogenetically characterized oral SCC and SCC from other sites of head and neck region, in order to define the molecular consequence of chromosomal regions commonly involved in structural rearrangements, such as centromeric and pericentromeric rearrangements, homogeneously staining regions in chromosomal band 11q13 and other chromosome loci. From these studies, it could be concluded that the essential outcome of near-centromeric or centromeric rearrangements is genomic imbalances, i.e., loss or gain of cancer-associated genes. For instance, target regions for deletions in 1p and 8p have been identified. Characterization of hsr, a cytogenetic sign of gene amplification, has shown that hsr in these neoplasms almost always derives from 11q13 DNA sequences, that such amplicons always include the CCND1 gene, and that the amplification is often concomitant with loss of the distal part of 11q and with the overrepresentation of distal 3q.

Frequent finding of comparative genomic hybridization (CGH) and allelic imbalance studies
Molecular genetic studies of oral SCC have been focused on the identification of tumor suppressor gene loci and amplified oncogenes. Earlier LOH studies focused on specific chromosome segments have pointed out the frequent loss of alleles from 3p, 8p, 9p, chromosome 13 and 17p in head and neck SCC, including oral SCC. A number of recent studies using allelotyping and comparative genomic hybridization (CGH) indicate that head and neck SCCs display massive and widespread genomic imbalances and that certain chromosome segment are lost more often than others. These studies confirmed the frequent deletion and LOH from 3p, 9p, 13q,and 17p, detected in more than 50% of the cases. Furthermore, deletions in 3q, 4p, 4q, 5q, 6p, 6q, 8p, 8q, 11q, 14q, 17q, 18q, and 20p have been shown in significant subsets.

Cytogenetics Molecular Candidate tumor suppressor genes (TSG) in frequently deleted chromosome region

Chromosomal arm 3p: Loss of 3p material, in particular 3p13-p21, p21-23, and p25, is a common genetic change shared by several types of carcinomas. Several tumor suppressor genes have been mapped to these regions. Among them, two genes, i.e., FHIT in 3p14.2 and VHL in 3p25-26, were studied for the presence of inactivation mutations in oral SCC. The finding of alterations of FHIT in oral precancerous lesions and SCC supports the pathogenetic role of FHIT in oral SCC carcinogenesis. However, very little evidence for the involvement of VHL in oral SCC could be observed.
Chromosome arms 4p and 4q: No TSG in these chromosomal arms has been identified in oral SCC so far.
Chromosome arm 5q: APC located at 5q21 is a TSG important for familial colon cancer and sporadic colon cancer. Some studies support the involvement of APC in oral SCC, whereas others do not.
Chromosome arms 6p and 6q: No TSG in these chromosomal arms has been identified in oral SCC so far.
Chromosome arm 8p: 8p12 and 8p22 are frequently deleted in oral SCC. A recent study using RT-PCR showed reduced expression of FEZ1/LZTS1, a candidate tumor suppressor gene mapped to 8p22, which may contribute to the development of oral SCC. No other genes in these regions have been investigated.
Chromosome arm 9p: CDKN2A (a.k.a. p16), a cell cycle regulatory gene, located at 9p21, is frequently down regulated through homozygous deletion or hypermethylation in oral SCC.
Chromosome arms 11p and 11q: 11p14 and 11q14­qter were reported to be lost in a fraction of oral SCC. However, no TSG has been identified yet.
Chromosome arm 13q: Some studies showed LOH of RB1, mapped to 13q14, in a fraction of oral SCC. Furthermore, lack of expression of RB1 in about half of cases has been reported in one immunohistochemistry study.
Chromosome arm 17p: Loss of 17p is not very common at the cytogenetic level. However, such deletions are frequent at LOH studies. The prevalence of TP53 mutation and expression of a mutated protein has been reported in 40-60% of oral SCC. Expression of mutated TP53 in oral premalignant lesions may indicate malignant transformation. Especially, expression above the basal cell layer has been highly predictive of malignant development. A number of studies have shown that TP53 mutation is associated with increased risk of locoregional recurrence and poor outcome.
Chromosome arm 18q: No target gene important for oral SCC has been reported for this chromosome arm.

Frequent amplification of oncogenes in homogeneously staining regions and amplified chromosome segments

Hsr in 11q13 and CCND1 amplification: The second most common structural rearrangement identified in oral SCC is hsr, a cytogenetic sign of gene amplification, found in about 25% of cytogenetically aberrant tumors. Approximately one half of the hsrs were found in chromosomal band 11q13. FISH studies have demonstrated that hsr in 11q13, as well as at other chromosomal loci, almost always originates from 11q13 DNA sequences and that the amplification then always includes CCND1. These findings are in agreement with extensive molecular investigations by various techniques, indicating that CCND1 is the prime target in the amplification process and important for oral SCC development. A recent study has shown that Cyclin D1 overexpression alone can induce extension of the replicate life span of normal keratinocytes, and the combination of cyclin D1 overexpression and TP53 inactivation led to their immortalization. Furthermore, several molecular studies have shown that CCND1 amplification and/or overexpression is a prognostic marker for disease free survival.
Chromosome arm 3q: A number of oncogenes, such as LAZ3/BCL6, PIK3CA, DCUN1D1/SCCRO, telomerase RNA and AIS gene, map to 3q26-28, a frequently gained chromosomal segment shown by cytogenetic and CGH studies. Among them, SCCRO and PIK3CA may play a role in the pathogenesis of oral SCC through amplification at 3q26, and SCCRO appears to be a significant predictor of regional metastasis and may be a marker for tumor aggressiveness and clinical outcome.
Chromosome arm 7p: Gain of part of or the entire chromosome 7 has been a common finding in oral SCC. Epidermal growth factor receptor EGFR and the insulin like growth factors IGFB1 and IGFB2 are three potentially interesting genes located in 7p13-22. EGFR has been extensively investigated in oral SCC, particularly with respect to therapeutic targeting of these neoplasms. The results of these studies suggest that amplification of the EGFR gene occurs at a relatively early stage of the development of oral SCC and a high level of EGFR gene expression probably plays an important role in the progression to invasive cancer.
Chromosome arm 8q: Gain of 8q material through the formation of isochromosome i(8q) and unbalanced structural rearrangements are the most common structural change in oral SCC. Several genes of interest, such as MYC and PTK2, are localized at 8q23-24. However, as yet, no evidence for the involvement of these genes has been reported in oral SCC.

Bibliography

Amplification of cyclin D1 in squamous cell carcinoma of the head and neck and the prognostic value of chromosomal abnormalities and cyclin D1 overexpression.
Akervall JA, Michalides RJ, Mineta H, Balm A, Borg A, Dictor MR, Jin Y, Loftus B, Mertens F, Wennerberg JP
Cancer. 1997 ; 79 (2) : 380-389.
PMID 9010112
 
Distinct patterns of chromosomal alterations in high- and low-grade head and neck squamous cell carcinomas.
Bockmü U, Schwendel A, Dietel M, Petersen I
Cancer research. 1996 ; 56 (23) : 5325-5329.
PMID 8968077
 
Patterns of chromosomal alterations in metastasizing and nonmetastasizing primary head and neck carcinomas.
Bockmühl U, Petersen S, Schmidt S, Wolf G, Jahnke V, Dietel M, Petersen I
Cancer research. 1997 ; 57 (23) : 5213-5216.
PMID 9393736
 
The role of novel oncogenes squamous cell carcinoma-related oncogene and phosphatidylinositol 3-kinase p110alpha in squamous cell carcinoma of the oral tongue.
Estilo CL, O-Charoenrat P, Ngai I, Patel SG, Reddy PG, Dao S, Shaha AR, Kraus DH, Boyle JO, Wong RJ, Pfister DG, Huryn JM, Zlotolow IM, Shah JP, Singh B
Clinical cancer research : an official journal of the American Association for Cancer Research. 2003 ; 9 (6) : 2300-2306.
PMID 12796399
 
Cyclin D1 amplification correlates with early recurrence of squamous cell carcinoma of the tongue.
Fujii M, Ishiguro R, Yamashita T, Tashiro M
Cancer letters. 2001 ; 172 (2) : 187-192.
PMID 11566495
 
Centromeric breakage as a major cause of cytogenetic abnormalities in oral squamous cell carcinoma.
Hermsen MA, Joenje H, Arwert F, Welters MJ, Braakhuis BJ, Bagnay M, Westerveld A, Slater R
Genes, chromosomes & cancer. 1996 ; 15 (1) : 1-9.
PMID 8824719
 
Mutations of the APC, beta-catenin, and axin 1 genes and cytoplasmic accumulation of beta-catenin in oral squamous cell carcinoma.
Iwai S, Katagiri W, Kong C, Amekawa S, Nakazawa M, Yura Y
Journal of cancer research and clinical oncology. 2005 ; 131 (12) : 773-782.
PMID 16163548
 
Cytogenetic abnormalities in 106 oral squamous cell carcinomas.
Jin C, Jin Y, Wennerberg J, Annertz K, Enoksson J, Mertens F
Cancer genetics and cytogenetics. 2006 ; 164 (1) : 44-53.
PMID 16364762
 
FISH characterization of head and neck carcinomas reveals that amplification of band 11q13 is associated with deletion of distal 11q.
Jin Y, Höglund M, Jin C, Martins C, Wennerberg J, Akervall J, Mandahl N, Mitelman F, Mertens F
Genes, chromosomes & cancer. 1998 ; 22 (4) : 312-320.
PMID 9669669
 
Cytogenetic and fluorescence in situ hybridization characterization of chromosome 1 rearrangements in head and neck carcinomas delineate a target region for deletions within 1p11-1p13.
Jin Y, Jin C, Wennerberg J, Mertens F, Höglund M
Cancer research. 1998 ; 58 (24) : 5859-5865.
PMID 9865746
 
Nonrandom chromosome abnormalities in short-term cultured primary squamous cell carcinomas of the head and neck.
Jin Y, Mertens F, Jin C, Akervall J, Wennerberg J, Gorunova L, Mandahl N, Heim S, Mitelman F
Cancer research. 1995 ; 55 (14) : 3204-3210.
PMID 7606742
 
High frequency of p53 mutations in human oral epithelial dysplasia and primary squamous cell carcinoma detected by yeast functional assay.
Kashiwazaki H, Tonoki H, Tada M, Chiba I, Shindoh M, Totsuka Y, Iggo R, Moriuchi T
Oncogene. 1997 ; 15 (22) : 2667-2674.
PMID 9400993
 
Expression of cyclin D1 is correlated with poor prognosis in patients with areca quid chewing-related oral squamous cell carcinomas in Taiwan.
Kuo MY, Lin CY, Hahn LJ, Cheng SJ, Chiang CP
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1999 ; 28 (4) : 165-169.
PMID 10235369
 
Cyclin-D1-gene amplification is a more potent prognostic factor than its protein over-expression in human head-and-neck squamous-cell carcinoma.
Kyomoto R, Kumazawa H, Toda Y, Sakaida N, Okamura A, Iwanaga M, Shintaku M, Yamashita T, Hiai H, Fukumoto M
International journal of cancer. Journal international du cancer. 1997 ; 74 (6) : 576-581.
PMID 9421351
 
Chromosome 13q deletion mapping in head and neck squamous cell carcinomas: identification of two distinct regions of preferential loss.
Maestro R, Piccinin S, Doglioni C, Gasparotto D, Vukosavljevic T, Sulfaro S, Barzan L, Boiocchi M
Cancer research. 1996 ; 56 (5) : 1146-1150.
PMID 8640775
 
Loss of heterozygosity at 5q21-22 (adenomatous polyposis coli gene region) in oral squamous cell carcinoma is common and correlated with advanced disease.
Mao EJ, Schwartz SM, Daling JR, Beckmann AM
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1998 ; 27 (7) : 297-302.
PMID 9725566
 
Frequent microsatellite alterations at chromosomes 9p21 and 3p14 in oral premalignant lesions and their value in cancer risk assessment.
Mao L, Lee JS, Fan YH, Ro JY, Batsakis JG, Lippman S, Hittelman W, Hong WK
Nature medicine. 1996 ; 2 (6) : 682-685.
PMID 8640560
 
Fluorescent in situ hybridisation (FISH) characterisation of pericentromeric breakpoints on chromosome 5 in head and neck squamous cell carcinomas.
Martins C, Jin Y, Jin C, Wennerberg J, Höglund M, Mertens F
European journal of cancer (Oxford, England : 1990). 1999 ; 35 (3) : 498-501.
PMID 10448306
 
Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck.
Michalides R, van Veelen N, Hart A, Loftus B, Wientjens E, Balm A
Cancer research. 1995 ; 55 (5) : 975-978.
PMID 7867006
 
Cyclin D1 overexpression correlates with poor prognosis in patients with tongue squamous cell carcinoma.
Mineta H, Miura K, Takebayashi S, Ueda Y, Misawa K, Harada H, Wennerberg J, Dictor M
Oral oncology. 2000 ; 36 (2) : 194-198.
PMID 10745172
 
Quantitation of epidermal growth factor receptor gene amplification by competitive polymerase chain reaction in pre-malignant and malignant oral epithelial lesions.
Nagatsuka H, Ishiwari Y, Tsujigiwa H, Nakano K, Nagai N
Oral oncology. 2001 ; 37 (7) : 599-604.
PMID 11564582
 
Alterations of Rb, p16(INK4A) and cyclin D1 in the tumorigenesis of oral squamous cell carcinomas.
Nakahara Y, Shintani S, Mihara M, Kiyota A, Ueyama Y, Matsumura T
Cancer letters. 2000 ; 160 (1) : 3-8.
PMID 11098077
 
Allelotype of head and neck squamous cell carcinoma.
Nawroz H, van der Riet P, Hruban RH, Koch W, Ruppert JM, Sidransky D
Cancer research. 1994 ; 54 (5) : 1152-1155.
PMID 8118797
 
Allelic loss of chromosome 13q14.3 in human oral cancer: correlation with lymph node metastasis.
Ogawara K, Miyakawa A, Shiba M, Uzawa K, Watanabe T, Wang XL, Sato T, Kubosawa H, Kondo Y, Tanzawa H
International journal of cancer. Journal international du cancer. 1998 ; 79 (4) : 312-317.
PMID 9699520
 
Down-regulation of FEZ1/LZTS1 gene with frequent loss of heterozygosity in oral squamous cell carcinomas.
Ono K, Uzawa K, Nakatsuru M, Shiiba M, Mochida Y, Tada A, Bukawa H, Miyakawa A, Yokoe H, Tanzawa H
International journal of oncology. 2003 ; 23 (2) : 297-302.
PMID 12851677
 
Location of candidate tumour suppressor gene loci at chromosomes 3p, 8p and 9p for oral squamous cell carcinomas.
Partridge M, Emilion G, Pateromichelakis S, Phillips E, Langdon J
International journal of cancer. Journal international du cancer. 1999 ; 83 (3) : 318-325.
PMID 10495423
 
The FHIT gene in oral squamous cell carcinoma: allelic imbalance is frequent but cDNA aberrations are uncommon.
Pateromichelakis S, Lee G, Langdon JD, Partridge M
Oral oncology. 2000 ; 36 (2) : 180-188.
PMID 10745170
 
Allelic imbalance on chromosome 3p in oral dysplastic lesions: an early event in oral carcinogenesis.
Roz L, Wu CL, Porter S, Scully C, Speight P, Read A, Sloan P, Thakker N
Cancer research. 1996 ; 56 (6) : 1228-1231.
PMID 8640803
 
Amplification and overexpression of epidermal growth factor receptor gene in human oropharyngeal cancer.
Saranath D, Panchal RG, Nair R, Mehta AR, Sanghavi VD, Deo MG
European journal of cancer. Part B, Oral oncology. 1992 ; 28B (2) : 139-143.
PMID 1306731
 
Genetic aberrations in oral or head and neck squamous cell carcinoma 2: chromosomal aberrations.
Scully C, Field JK, Tanzawa H
Oral oncology. 2000 ; 36 (4) : 311-327.
PMID 10899669
 
Abrogation of IL-6-mediated JAK signalling by the cyclopentenone prostaglandin 15d-PGJ(2) in oral squamous carcinoma cells.
Siavash H, Nikitakis NG, Sauk JJ
British journal of cancer. 2004 ; 91 (6) : 1074-1080.
PMID 15316561
 
Abnormalities of the FHIT gene in human oral carcinogenesis.
Tanimoto K, Hayashi S, Tsuchiya E, Tokuchi Y, Kobayashi Y, Yoshiga K, Okui T, Kobayashi M, Ichikawa T
British journal of cancer. 2000 ; 82 (4) : 838-843.
PMID 10732756
 
Expression of adenomatous polyposis coli (APC) in tumorigenesis of human oral squamous cell carcinoma.
Tsuchiya R, Yamamoto G, Nagoshi Y, Aida T, Irie T, Tachikawa T
Oral oncology. 2004 ; 40 (9) : 932-940.
PMID 15380172
 
Functional evidence for involvement of multiple putative tumor suppressor genes on the short arm of chromosome 3 in human oral squamous cell carcinogenesis.
Uzawa N, Yoshida MA, Hosoe S, Oshimura M, Amagasa T, Ikeuchi T
Cancer genetics and cytogenetics. 1998 ; 107 (2) : 125-131.
PMID 9844607
 
Recurrent cytogenetic abnormalities in squamous cell carcinomas of the head and neck region.
Van Dyke DL, Worsham MJ, Benninger MS, Krause CJ, Baker SR, Wolf GT, Drumheller T, Tilley BC, Carey TE
Genes, chromosomes & cancer. 1994 ; 9 (3) : 192-206.
PMID 7515662
 
Epigenetic changes of tumor suppressor genes, P15, P16, VHL and P53 in oral cancer.
Yeh KT, Chang JG, Lin TH, Wang YF, Tien N, Chang JY, Chen JC, Shih MC
Oncology reports. 2003 ; 10 (3) : 659-663.
PMID 12684640
 

Citation

This paper should be referenced as such :
Jin, C ; Jin, Y
Head, neck: Oral squamous cell carcinoma
Atlas Genet Cytogenet Oncol Haematol. 2007;11(1):46-49.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Tumors/OralSquamCellID5368.html


Other genes implicated (Data extracted from papers in the Atlas) [ 77 ]

Genes ADAM10 ADRB2 AGER ANXA1 BCL2L14 CALR CAPG CASP7 CAV1 CCNA1
CCNA1 CCNB1 CCR1 CD109 CD151 CD82 CLDN7 COL16A1 CRK CRYAB
CST6 CTGF DEFB1 DKK3 DND1 ECT2 EIF4B ERBB2 FABP5 FAT1
FGFR1 GALNT6 HELLS HMGA2 HNRNPD ING1 IRS2 KLF4 KLK7 KLK8
LATS1 LDB1 LOX LOXL2 LOXL4 LZTS1 RIOX2 MIR200C MIR125B1 MIR125B2
MMP26 MMP26 MMP2 MYEOV NME1 NNMT NR4A1 ORAOV1 PDCD5 PERP
PHLDA1 PLAUR PRDX4 PTBP1 PTPRA RASSF2 ROR2 S100A2 S100A4 S100A7
SNAI1 STMN1 TGFBR3 TPX2 TRIO VCAN VCP

External links

arrayMap Topo ( C03,C4,C04,C5,C05,C6,C06) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Other databaseICGC Data Portal - [ORCA-IN] Oral Cancer - IN
Disease databaseHead and Neck: Oral squamous cell carcinoma
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed


© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Tue Mar 14 13:56:55 CET 2017


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.