Loss of heterozygosity on chromosome arms 3p and 6q in microdissected adenocarcinomas of the uterine cervix and adenocarcinoma in situ

Acevedo, Mariana; Henríquez, Berta; Emmert‐Buck, Michael R.; Chuaqui, Rodrigo F.

doi:10.1002/cncr.10275

Cited by 30 publications

(23 citation statements)

References 26 publications

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“…Indeed, aberrations in NLJ-003 locus were detected in 81.3% and in NL3-001 in 71.9% cases. Furthermore, aberrations in at least one of these loci were detected in 90.6% cases that is significantly higher than was reported before for 3p21.3 (23-57%) and FHIT (30-58%) (Wistuba et al, 1997;Muller et al, 1998;Helland et al, 2000;Herzog et al, 2001;Acevedo et al, 2002).…”

Section: Discussionmentioning

confidence: 61%

“…Moreover, 3p and 6p were also involved at the early precancer stages and during progression of cervical intraepithelial neoplasia to invasive cervical cancer (Larson et al, 1997b;Wistuba et al, 1997;Fouret et al, 1998;Guo et al, 1998Guo et al, , 2000Guo et al, , 2001Umayahara et al, 2002). Different studies reported various 3p LOH rates in the range 50-76% (Wistuba et al, 1997;Braga et al, 1999;Guo et al, 2000;Helland et al, 2000;Herzog et al, 2001;Acevedo et al, 2002). Several reports suggested that the most frequently affected in CC regions were located in 3p21.3-p22 region and near FHIT gene in 3p14.2 (Wistuba et al, 1997;Muller et al, 1998;Helland et al, 2000;Herzog et al, 2001;Acevedo et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Different studies reported various 3p LOH rates in the range 50-76% (Wistuba et al, 1997;Braga et al, 1999;Guo et al, 2000;Helland et al, 2000;Herzog et al, 2001;Acevedo et al, 2002). Several reports suggested that the most frequently affected in CC regions were located in 3p21.3-p22 region and near FHIT gene in 3p14.2 (Wistuba et al, 1997;Muller et al, 1998;Helland et al, 2000;Herzog et al, 2001;Acevedo et al, 2002). We have found recently that two regions in 3p21.3 (centromeric -C or LUCA and telomeric -T or AP20) were frequently deleted in major human malignancies (Braga et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Deletion mapping using quantitative real-time PCR identifies two distinct 3p21.3 regions affected in most cervical carcinomas

et al. 2003

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We report chromosome 3p deletion mapping of 32 cervical carcinoma (CC) biopsies using 26 microsatellite markers located in frequently deleted 3p regions to detect loss of heterozygosity and homozygous loss. In addition, two STS markers (NLJ-003 and NL3-001) located in the 3p21.3 telomeric (3p21.3T) and 3p21.3 centromeric (3p21.3C) regions, respectively, were used for quantitative real-time PCR as TaqMan probes. We show that quantitative real-time PCR is reliable and sensitive and allows discriminating between 0, 1 and 2 marker copies per human genome. For the first time, frequent (five of 32 cases, i.e. 15.6%) homozygous deletions were demonstrated in CCs in both 3p21.3T and 3p21.3C regions. The smallest region homozygously deleted in 3p21.3C was located between D3S1568 (CACNA2D2 gene) and D3S4604 (SEMA3F gene) and contains 17 genes previously defined as lung cancer candidate Tumor suppressor genes (TSG(s)). The smallest region homozygously deleted in 3p21.3T was flanked by D3S1298 and NL1-024 (D3S4285), excluding DLEC1 and MYD88 as candidate TSGs involved in cervical carcinogenesis. Overall, this region contains five potential candidates, namely GOLGA4, APRG1, ITGA9, HYA22 and VILL, which need to be analysed. The data showed that aberrations of either NLJ-003 or NL3-001 were detected in 29 cases (90.6%) and most likely have a synergistic effect (Po0.01). The study also demonstrated that aberrations in 3p21.3 were complex and in addition to deletions, may involve gene amplification as well. The results strongly suggest that 3p21.3T and 3p21.3C regions harbor genes involved in the origin and/or development of CCs and imply that those genes might be multiple TSG(s).

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Deletion mapping using quantitative real-time PCR identifies two distinct 3p21.3 regions affected in most cervical carcinomas

et al. 2003

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“…3 and references therein); however, a possible target tumor suppressor gene (TSG) remains to be identified from this region. Interestingly, several cancer types, including breast, 4 gastric 5 and cervical cancer 6 as well as a variety of hematopoietic malignancies 7,8 have common regions of deletion at 6q that coincide with that identified in prostate cancer, suggesting that a putative target TSG at 6q may be shared by at least some of these malignancies.…”

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confidence: 90%

Chromosomal deletion, promoter hypermethylation and downregulation of FYN in prostate cancer

Sørensen¹,

Borre²,

Ørntoft³

et al. 2007

Intl Journal of Cancer

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Loss of heterozygosity (LOH) at 6q is a frequent chromosomal aberration in prostate adenocarcinoma; however, a possible target gene remains to be identified. Key words: prostate cancer; FYN tyrosine kinase; tumor suppressor gene; hypermethylation; loss of heterozygosity Development and progression of prostate cancer is associated with the accumulation of complex genetic and epigenetic aberrations.1 Recently, we identified common allelic imbalance at 6q14-6q22 in prostate cancer by a genome-wide loss of heterozygosity (LOH) analysis using high-density single nucleotide polymorphism (SNP) microarrays.2 Other groups have earlier reported similar regions of deletion/LOH at 6q in prostate cancer (Ref. 3 and references therein); however, a possible target tumor suppressor gene (TSG) remains to be identified from this region. Interestingly, several cancer types, including breast, 4 gastric 5 and cervical cancer 6 as well as a variety of hematopoietic malignancies 7,8 have common regions of deletion at 6q that coincide with that identified in prostate cancer, suggesting that a putative target TSG at 6q may be shared by at least some of these malignancies.Retroviral tagging has proved to be a powerful cancer gene discovery tool, with many genes identified as common integration sites in retrovirus-induced murine leukemia/lymphoma models, playing critical roles also in human cancers, including solid tumors.9,10 On the basis of this and substantiated by the overlapping deletions at 6q found in both prostate cancer and various types of human hematopoietic malignancies, we envisaged that retroviral tags from murine leukemia/lymphoma models might help the search for a candidate TSG at 6q. Hence, in this study, to identify a new possible TSG in prostate cancer, we hypothesized that a gene in the main LOH region at 6q14-6q22 that is both (i) transcriptionally downregulated in prostate cancer compared to nonmalignant prostate tissues and (ii) disrupted by retroviral insertion in murine hematopoietic cancer models, would provide a good candidate for further analysis. Accordingly, the SRC family tyrosine kinase gene FYN at 6q21 was selected for further investigation.FYN contains an N-terminal SH4 myristoylation and palmitoylation domain, which targets the protein to the inner plasma membrane. It is followed by a unique sequence, distinguishing FYN from other SRC family members, 2 protein-protein interaction domains (SH3 and SH2), a kinase domain (SH1) and a C-terminal negative regulatory domain.11 The 2 known major splice forms, FYN(B) (aka P59FynB) using exon 7A and FYN(T) (aka P59FynT) using exon 7B, 11 differ in a linker region between SH2 and SH1 that extends into the kinase domain, causing moderate regulatory differences between these isoforms.12 FYN(B) is highly expressed in brain, and hematopoietic cells express mainly FYN(T), while most other tissues express both isoforms.11 A variant mRNA lacking exon 7 (FYN(D7)) exists in blood cells, but the corresponding endogenous protein has not been documented. 13The biological fun...

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“…Loss of heterozygosity in 3p and reduced FHIT expression have been reported in cervical cancer and precancer lesions (Wistuba et al, 1997;Birrer et al, 1999;Chung et al, 2000;Connolly et al, 2000;Guo et al, 2001;Acevedo et al, 2002) but, because of small sample numbers or because of differences in the 3p loci selected for LOH analysis, it is not clear if any regions of 3p are consistently deleted or if reduction in FHIT protein level is dependent on these deletions. In most studies, the HR HPV genotyping was also incomplete.…”

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confidence: 99%

The role of human papillomavirus type 16 and the fragile histidine triad gene in the outcome of cervical neoplastic lesions

Terry

Londesborough

et al. 2004

Br J Cancer

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The presence of high-risk human papillomavirus, loss of heterozygosity on chromosome 3p and fragile histidine triad gene expression were assessed as potential markers of cancer and CIN progression in 83 cervical cancers and 74 cervical intraepithelial neoplasia grade 1 lesions. Human papillomavirus type 16 was an indicator of vascular involvement in cancers. Loss of heterozygosity, especially in the fragile histidine triad gene intron 5, was an indicator of high-grade tumours, greater tumour depth and lymph node involvement. Abnormal fragile histidine triad gene expression was more frequent in cervical intraepithelial neoplasia grade 1 lesions with increased risk of disease progression.

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Loss of heterozygosity on chromosome arms 3p and 6q in microdissected adenocarcinomas of the uterine cervix and adenocarcinoma in situ

Cited by 30 publications

References 26 publications

Deletion mapping using quantitative real-time PCR identifies two distinct 3p21.3 regions affected in most cervical carcinomas

Deletion mapping using quantitative real-time PCR identifies two distinct 3p21.3 regions affected in most cervical carcinomas

Chromosomal deletion, promoter hypermethylation and downregulation of FYN in prostate cancer

The role of human papillomavirus type 16 and the fragile histidine triad gene in the outcome of cervical neoplastic lesions

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