Advanced‐stage cervical carcinomas are defined by a recurrent pattern of chromosomal aberrations revealing high genetic instability and a consistent gain of chromosome arm 3q

Heselmeyer, Kerstin; Macville, Merryn; Blegen, Harald; Hellström, Ann‐Cathrin; Shah, Keerti V.; Auer, Gert; Ried, Thomas

doi:10.1002/(sici)1098-2264(199708)19:4<233::aid-gcc5>3.3.co;2-k

Cited by 89 publications

(140 citation statements)

References 14 publications

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“…These data support gain of 3q as an important event in the oncogenesis of HPV-related SCCs since, in a previous study, we have shown that a similar proportion of stage 1b HPV-positive cervical SCCs harbour 3q gain (Allen et al, 2000). Gain of 3q has also been detected by others in cervical SCCs (Heselmeyer et al, 1996(Heselmeyer et al, , 1997bDellas et al, 1999;Kirchoff et al, 1999) and in HPV-positive SCC of the anus and its precursor lesions (Heselmeyer et al, 1997a;Haga et al, 2001). Further, we were able to map the smallest region of gain in vulvar SCCs to 3q22 -25, whilst our previous series of cervical cancers showed the smallest area of gain to be 3q24 -26 (Allen et al, 2000).…”

Section: Discussionsupporting

confidence: 87%

“…Furthermore, two of the microsatellite markers showing LOH which were used in the previous studies were mapped to the region of 3p24, which was the smallest Comparative genomic hybridisation in vulvar cancer DG Allen et al region of chromosome loss detected by CGH in the current study. Loss of 3p is also frequently seen in cervical SCC, by CGH and LOH analysis (Heselmeyer et al, 1996(Heselmeyer et al, , 1997bLarson et al, 1997;Wistuba et al, 1997;Kersemaekers et al, 1998;Steenbergen et al, 1998;Dellas et al, 1999;Kirchoff et al, 1999;Allen et al, 2000). Loss of 11q has been documented in cervical and other malignancies not related to HPV infection, including breast, colorectal and ovarian cancers and malignant melanoma (Hampton et al, 1994;Kersemaekers et al, 1998;Allen et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

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Genetic aberrations detected by comparative genomic hybridisation in vulvar cancers

Hammet

et al. 2002

Br J Cancer

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Squamous cell carcinoma of the vulva is a disease of significant clinical importance, which arises in the presence or absence of human papillomavirus. We used comparative genomic hybridisation to document non-random chromosomal gains and losses within human papillomavirus positive and negative vulvar cancers. Gain of 3q was significantly more common in human papillomavirus-positive cancers compared to human papillomavirus-negative cancers. The smallest area of gain was 3q22 -25, a chromosome region which is frequently gained in other human papillomavirus-related cancers. Chromosome 8q was more commonly gained in human papillomavirus-negative compared to human papillomavirus-positive cancers. 8q21 was the smallest region of gain, which has been identified in other, non-human papillomavirus-related cancers. Chromosome arms 3p and 11q were lost in both categories of vulvar cancer. This study has demonstrated chromosome locations important in the development of vulvar squamous cell carcinoma. Additionally, taken together with previous studies of human papillomaviruspositive cancers of other anogenital sites, the data indicate that one or more oncogenes important in the development and progression of human papillomavirus-induced carcinomas are located on 3q. The different genetic changes seen in human papillomavirus-positive and negative vulvar squamous cell carcinomas support the clinicopathological data indicating that these are different cancer types.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Genetic aberrations detected by comparative genomic hybridisation in vulvar cancers

Hammet

et al. 2002

Br J Cancer

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“…This genomic amplification is now recognized as an underlying cause of many low-frequency genetic events (being amplified in 10-20% of the cases) in pancreatic adenocarcinoma (Griffin et al, 1994;Ruggeri et al, 1998;Altomare et al, 2003). The 19q13 locus is also amplified in several other cancers such as follicular lymphoma (Werner et al, 1997), Mantle cell lymphoma (Werner et al, 1997), Burkitt's lymphoma, small-cell lung cancer (Ried et al, 1994;Petersen et al, 1997), non-small-cell lung cancer (Petersen et al, 1997;Bjorkqvist et al, 1998), breast carcinoma (Kallioniemi et al, 1994), and uterine cervix cancer (Heselmeyer et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), localized on the 19q13 amplicon, is associated with tumorigenesis

et al. 2006

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The 19q13 amplicon in pancreatic cancer cells contains a novel pancreatic differentiation 2 (PD2) gene (accession number AJ401156), which was identified by differential screening analysis. PD2 is the human homologue of the RNA polymerase II-associated factor 1 (hPaf1). In yeast, Paf1 is part of the transcription machinery, acting as a docking protein in between the complexes Rad6-Bre1, COMPASS-Dot1p, and the phosphorylated carboxyl terminal domain of the RNA polymerase II. As such, Paf1 is directly involved in transcription elongation via histone H2B ubiquitination and histone H3 methylation. The PD2 sequence is highly conserved from Drosophila to humans with up to 98% identity between rodent and human, suggesting the functional importance of PD2/ hPaf1 to maintain cellular homeostasis. PD2 is a modular protein composed of RNA recognition motif, DEADboxes, an aspartic/serine (DS)-domain, a regulator of the chromosome condensation domain and myc-type helixloop-helix domains. Our results further showed that PD2 is a nuclear 80 kDa protein, which interacts with RNA polymerase II. In addition, we have demonstrated that the overexpression of PD2 in the NIH 3T3 cells result in enhanced growth rates in vitro and tumor formation in vivo. Altogether, this paper presents strong evidence that the overexpression of PD2/hPaf1 is involved in cancer development.

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“…CGH is a well-suited tool to compare chromosomal aberrations with additional pertinent characteristics of specific tumours, such as histology, DNA ploidy and immunohistochemistry Ried et al, 1996). We have recently established a phenotype-genotype correlation in the genesis of HPV-positive squamous cell carcinomas of the cervix uteri (Heselmeyer et al, , 1997. We observed a characteristic pattern of genetic and phenotypic changes that were specific for cervical carcinogenesis: the gain of the long arm of chromosome 3 occurred in virtually all HPV-positive, aneuploid invasive carcinomas; and low expression of p53 was accompanied by high levels of p21/WAF-1.…”

mentioning

confidence: 99%

A recurrent pattern of chromosomal aberrations and immunophenotypic appearance defines anal squamous cell carcinomas

Heselmeyer

Manoir²,

Blegen³

et al. 1997

Br J Cancer

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Summary Squamous cell carcinomas of the anus are rare neoplasias that account for about 3% of large bowel tumours. Infections with human papillomaviruses are frequently detected in these cancers, suggesting that pathogenic pathways in anal carcinomas and in carcinomas of the uterine cervix are similar. Little is known regarding recurrent chromosomal aberrations in this subgroup of squamous cell carcinomas. We have applied comparative genomic hybridization to identify chromosomal gains and losses in 23 cases of anal carcinomas.A non-random copy number increase of chromosomes 17 and 19, and chromosome arm 3q was observed. Consistent losses were mapped to chromosome arms 4p, 11q, 13q and 18q. A majority of the tumours were aneuploid, and most of them showed increased proliferative activity as determined by staining for Ki-67 antigen. p53 expression was low or undetectable, and expression of p21/WAF-1 was increased in most tumours. Sixteen cancers were satisfactorily tested for the presence of HPV by consensus Li -primer polymerase chain reaction; nine were HPV positive, of which eight were positive for HPV 16.

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Advanced‐stage cervical carcinomas are defined by a recurrent pattern of chromosomal aberrations revealing high genetic instability and a consistent gain of chromosome arm 3q

Cited by 89 publications

References 14 publications

Genetic aberrations detected by comparative genomic hybridisation in vulvar cancers

Genetic aberrations detected by comparative genomic hybridisation in vulvar cancers

The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), localized on the 19q13 amplicon, is associated with tumorigenesis

A recurrent pattern of chromosomal aberrations and immunophenotypic appearance defines anal squamous cell carcinomas

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