Can a genetic signature for metastatic head and neck squamous cell carcinoma be characterised by comparative genomic hybridisation?

Patmore, H S; James, Nicholas; Cawkwell, Lynn; Macdonald, Alastair A.; Stafford, Nicholas D.; Greenman, John

doi:10.1038/sj.bjc.6601756

Cited by 14 publications

(12 citation statements)

References 17 publications

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“…Lymph node metastases usually have similar or additional genetic changes compared with PTs [2,10,11] . In the present study, we examined 23 PT and 9 NLNM samples by 1pter-p32, 3p22-p11, 8pter-q13, 11, 14q24-qter, 16 N22 1q, 3q, 4q, 8,12,18 1pter-p33, 10q, 14q23-qter, 16q N23 3q, 5p14-q12, 12pter-q21 1pter-p34, 4p, 14q23-qter, 16, 17p CGH combining tissue microdissection and DOP-PCR.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal Abnormalities Associated with Neck Nodal Metastasis in Nasopharyngeal Carcinoma

Yan¹,

Song

Wei-dong

et al. 2005

Tumor Biol

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Neck lymphatic metastasis represents the single most important clinical prognostic factor in nasopharyngeal carcinoma (NPC), but underlying genetic mechanisms remain ill defined. In this study 23 samples of primary tumor (PT) and 9 of neck lymph node metastasis (NLNM) obtained from NPC patients were analyzed by comparative genomic hybridization (CGH) coupled with tissue microdissection and degenerate oligonucleotide primer-polymerase chain reaction (DOP-PCR). A similar pattern of chromosomal abnormalities was seen in PT and NLNM, the common aberrations were gains on 5p, 12p, 12q and 18p and deletions on 1p, 3p, 9q, 14q, 17p and 16q. However, NLNMs, but not PTs, also exhibited frequent losses on 9p, 16p, 17q, 20q, 21p, 21q and 22q and gains on 8q and 8p. The most frequent unique aberration in NLNMs was loss on 16p, observed in 100% (9/9) NLNMs tested, as well as loss of 20q, observed in 77.8% of tumors tested. For the first time, we report that a gain on 8p and a loss at 20q is common to NLNMs. The analysis furthermore suggests that specific alterations, e.g. losses of 9p, 16p, 7q, 20q, 21p, 21q, 22q and gains on 8q and 8p are associated with NLNM of NPC, and that these alterations may be involved in the onset and/or progression of a metastatic phenotype.

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Section: Discussionmentioning

confidence: 99%

Chromosomal Abnormalities Associated with Neck Nodal Metastasis in Nasopharyngeal Carcinoma

Yan¹,

Song

Wei-dong

et al. 2005

Tumor Biol

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“…However, that study included a relatively small number of cases (8 cases) and did not compare the clonality between the genomic profiles of the primary and the metastasis in each case. In HNSCC, a few studies have analyzed the clonal relationship between primary and metastatic tumors [41]–[43]. However, since those studies used conventional metaphase CGH, which has limited resolution, details of genomic regions showing similarities and differences between the two sites were not fully characterized.…”

Section: Introductionmentioning

confidence: 99%

Genomic Profiling of Oral Squamous Cell Carcinoma by Array-Based Comparative Genomic Hybridization

et al. 2013

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We designed a study to investigate genetic relationships between primary tumors of oral squamous cell carcinoma (OSCC) and their lymph node metastases, and to identify genomic copy number aberrations (CNAs) related to lymph node metastasis. For this purpose, we collected a total of 42 tumor samples from 25 patients and analyzed their genomic profiles by array-based comparative genomic hybridization. We then compared the genetic profiles of metastatic primary tumors (MPTs) with their paired lymph node metastases (LNMs), and also those of LNMs with non-metastatic primary tumors (NMPTs). Firstly, we found that although there were some distinctive differences in the patterns of genomic profiles between MPTs and their paired LNMs, the paired samples shared similar genomic aberration patterns in each case. Unsupervised hierarchical clustering analysis grouped together 12 of the 15 MPT-LNM pairs. Furthermore, similarity scores between paired samples were significantly higher than those between non-paired samples. These results suggested that MPTs and their paired LNMs are composed predominantly of genetically clonal tumor cells, while minor populations with different CNAs may also exist in metastatic OSCCs. Secondly, to identify CNAs related to lymph node metastasis, we compared CNAs between grouped samples of MPTs and LNMs, but were unable to find any CNAs that were more common in LNMs. Finally, we hypothesized that subpopulations carrying metastasis-related CNAs might be present in both the MPT and LNM. Accordingly, we compared CNAs between NMPTs and LNMs, and found that gains of 7p, 8q and 17q were more common in the latter than in the former, suggesting that these CNAs may be involved in lymph node metastasis of OSCC. In conclusion, our data suggest that in OSCCs showing metastasis, the primary and metastatic tumors share similar genomic profiles, and that cells in the primary tumor may tend to metastasize after acquiring metastasis-associated CNAs.

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“…The prevailing view is that cancer cells acquire mutations late in tumor development that confer metastatic properties (1, 2), but experimental evidence of genes that are specifically mutated in human metastatic tumors is rare. In fact, comparative genomic hybridization (CGH) analysis of several different human tumor types has revealed a high degree of concordance between matched primary and metastatic tumors (3,4). Both gene expression profiling and CGH analysis of primary tumors can predict metastasis (5,6).…”

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confidence: 99%

Metastatic properties and genomic amplification of the tyrosine kinase gene ACK1

Horst

Degenhardt²,

Strelow³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

129

133

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Metastasis of primary tumors leads to a very poor prognosis for patients suffering from cancer. Although it is well established that not every tumor will eventually metastasize, it is less clear whether primary tumors acquire genetic alterations in a stochastic process at a late stage, which make them invasive, or whether genetic alterations acquired early in the process of tumor development drive primary tumor growth and determine whether this tumor is going to be metastatic. To address this issue, we tested genes identified in a large-scale comparative genomic hybridization analysis of primary tumor for their ability to confer metastatic properties on a cancer cell. We identified amplification of the ACK1 gene in primary tumors, which correlates with poor prognosis. We further show that overexpression of Ack1 in cancer cell lines can increase the invasive phenotype of these cells both in vitro and in vivo and leads to increased mortality in a mouse model of metastasis. Biochemical studies show that Ack1 is involved in extracellular matrix-induced integrin signaling, ultimately activating signaling processes like the activation of the small GTPase Rac. Taken cancer ͉ metastasis

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Can a genetic signature for metastatic head and neck squamous cell carcinoma be characterised by comparative genomic hybridisation?

Cited by 14 publications

References 17 publications

Chromosomal Abnormalities Associated with Neck Nodal Metastasis in Nasopharyngeal Carcinoma

Chromosomal Abnormalities Associated with Neck Nodal Metastasis in Nasopharyngeal Carcinoma

Genomic Profiling of Oral Squamous Cell Carcinoma by Array-Based Comparative Genomic Hybridization

Metastatic properties and genomic amplification of the tyrosine kinase gene ACK1

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