Microarray comparative genomic hybridization detection of chromosomal imbalances in uterine cervix carcinoma

Hidalgo, Alfredo; Baudis, Michael; Petersen, Iver; Arreola, Hugo; Piña, Patricia; Vázquez-Ortíz, Guelaguetza; Hernández, D.; González, José Luis Blanco; Lazos, Minerva; Lopez, R.S.; Pérez, Carlos; García, José; Vázquez, Karla Moreno; Alatorre, Brenda; Salcedo, Mauricio

doi:10.1186/1471-2407-5-77

Cited by 73 publications

(56 citation statements)

References 37 publications

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“…The general location of the CNV in band 4C6, in a region that has synteny to human chromosome 1p32.3-1p33, was intriguing given that several CGH studies have implicated loss in/near this chromosomal region in human tumors, including MM. In particular, D1S427-FAF1 was frequently lost in human uterine cervix carcinomas (25). This finding and the fact that Faf1 encodes a factor involved in the regulation of cell survival led us to pursue the possible involvement of this gene in MMs from Arf (ϩ/Ϫ) mice.…”

Section: Discussionmentioning

confidence: 99%

Activated TNF-α/NF-κB signaling via down-regulation of Fas-associated factor 1 in asbestos-induced mesotheliomas from Arf knockout mice

Altomare

Menges

Pei

et al. 2009

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

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The human CDKN2A locus encodes 2 distinct proteins, p16(INK4A) and p14(ARF) [mouse p19(Arf)], designated INK4A (inhibitor of cyclin dependent kinase 4) and ARF (alternative reading frame) here, that are translated from alternatively spliced mRNAs. Human ARF is implicated as a tumor suppressor gene, mainly in association with the simultaneous deletion of INK4A. However, questions remain as to whether loss of ARF alone is sufficient to drive tumorigenesis. Here, we report that mice deficient for Arf are susceptible to accelerated asbestos-induced malignant mesothelioma (MM). MMs arising in Arf (؉/؊) mice consistently exhibit biallelic inactivation of Arf, but, unexpectedly, do not acquire additional recurrent genetic alterations that we previously identified in asbestos-induced MMs arising in Nf2 (؉/؊) mice. Array CGH analysis was used to detect a recurrent deletion at chromosome 4C6 in MMs from Arf (؉/؊) mice. A candidate gene in this region, Faf1 (FAS-associated factor 1), was further explored, because it encodes a protein implicated in tumor cell survival and in the pathogenesis of some human tumor types. We confirmed hemizygous loss of Faf1 and down-regulation of Faf1 protein in a series of MMs from Arf (؉/؊) mice, and we then showed that Faf1 regulates TNF-␣-mediated NF-B signaling, a pathway previously implicated in asbestos-induced oncogenesis of human mesothelial cells. Collectively, these data indicate that Arf inactivation has a significant role in driving MM pathogenesis, and implicate Faf1 as a key component in the TNF-␣/NF-B signaling node that has now been independently implicated in asbestos-induced oncogenesis.array-CGH ͉ tumor suppressors T he CDKN2A (INK4a/ARF) locus encodes 2 distinct proteins translated from alternatively spliced mRNAs; p16(INK4A), designated as INK4A (inhibitor of cyclin dependent kinase 4) here, is encoded by exons 1␣, 2, and 3. The alternate product p14(ARF), dubbed ARF (alternative reading frame protein) here, is specified by exons 1␤, 2, and 3 (1, 2). Amino acid sequences of INK4A and ARF are unrelated, because exons 1␣ and 1␤ show no homology and exon 2/3 sequences are translated in different reading frames.The CDKN2A locus is among the most commonly mutated genomic sites in human cancer (2). Point mutations or deletions specifically affecting exon 1␣ of INK4A are not uncommon, although intragenic mutations affecting exon 1␤ of ARF are seldom, if ever, observed (2, 3). Overall, the high frequency of concurrent INK4A and ARF loss has made it difficult to assess the contribution of ARF to human tumorigenesis.We previously demonstrated that the CDKN2A locus is homozygously deleted in most malignant mesothelioma (MM) cell lines and in many MM tumor specimens (4). FISH analysis revealed a high incidence (Ϸ50 to 75%) of homozygous deletions in frozen MM specimens or MM cells cultured for Յ5 days (5, 6). Reexpression of INK4A in MM cells resulted in cell cycle arrest, cell death, as well as tumor suppression and regression (7). In contrast to the established role of INK4A, the i...

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Section: Discussionmentioning

confidence: 99%

Activated TNF-α/NF-κB signaling via down-regulation of Fas-associated factor 1 in asbestos-induced mesotheliomas from Arf knockout mice

Altomare

Menges

Pei

et al. 2009

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

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“…In contrast, the genetic changes associated with CIN and CxSCC have been extensively studied, most recently using array-based methods (Hidalgo et al, 2005;Wilting et al, 2006Wilting et al, , 2009Choi et al, 2007;Kloth et al, 2007;Scotto et al, 2008a, b).…”

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confidence: 99%

High-resolution genomic profiling of human papillomavirus-associated vulval neoplasia

et al. 2010

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BACKGROUND: The incidence of human papillomavirus-associated vulval neoplasia is increasing worldwide; yet the associated genetic changes remain poorly understood. METHODS: We have used single-nucleotide polymorphism microarray analysis to perform the first high-resolution investigation of genome-wide allelic imbalance in vulval neoplasia. Our sample series comprised 21 high-grade vulval intraepithelial neoplasia and 6 vulval squamous cell carcinomas, with paired non-lesional samples used to adjust for normal copy number variation. RESULTS: Overall the most common recurrent aberrations were gains at 1p and 20, with the most frequent deletions observed at 2q, 3p and 10. Copy-neutral loss of heterozygosity at 6p was a recurrent event in vulval intraepithelial neoplasia. The pattern of genetic alterations differed from the characteristic changes we previously identified in cutaneous squamous cell carcinomas. Vulval neoplasia samples did not exhibit gain at 5p, a frequent recurrent aberration in a series of cervical tumours analysed elsewhere using an identical protocol. CONCLUSION: This series of 27 vulval samples comprises the largest systematic genome-wide analysis of vulval neoplasia performed to date. Despite shared papillomavirus status and regional proximity, our data suggest that the frequency of certain genetic alterations may differ in vulval and cervical tumours.

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“…Similar situation might be observed for Parkin gene due to increased expression in CC. This could be supported because the 6q25 cytogenetic region in CC is not altered as happen for TP53 gene (33). To this respect, we could hypothesize that a new overexpression of Parkin gene could be involved in invasion cervical carcinogenesis.…”

Section: Discussionmentioning

confidence: 52%

Functional Analysis of the Cervical Carcinoma Transcriptome: Networks and New Genes Associated to Cancer

Salcedo¹,

Juárez-Méndez²,

Villegas-Ruíz³

et al. 2011

Computational Biology and Applied Bioinformatics

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Microarray comparative genomic hybridization detection of chromosomal imbalances in uterine cervix carcinoma

Cited by 73 publications

References 37 publications

Activated TNF-α/NF-κB signaling via down-regulation of Fas-associated factor 1 in asbestos-induced mesotheliomas from Arf knockout mice

Activated TNF-α/NF-κB signaling via down-regulation of Fas-associated factor 1 in asbestos-induced mesotheliomas from Arf knockout mice

High-resolution genomic profiling of human papillomavirus-associated vulval neoplasia

Functional Analysis of the Cervical Carcinoma Transcriptome: Networks and New Genes Associated to Cancer

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