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Background: The crucial event driving nasopharyngeal tumorigenesis is the hypermethylation of chromosome 3p-located tumor suppressor genes. This case-control study aims to investigate the methylation characteristics of RASSF1A, Blu, ADAMTS9 , and DLEC1 to potentially develop effective diagnostic biomarkers for nasopharyngeal carcinoma, either individually or in combination., Methods: The methylation of RASSF1A , Blu , ADAMTS9 , and DLEC1 in the collection of 93 biopsy samples and 100 healthy swab specimens were evaluated by Nested methylation-specific polymerase chain reaction. The strength of the correlation between candidate genes and nasopharyngeal carcinoma was estimated by the evaluation of odds ratios (ORs)., Results: Promoter hypermethylation of RASSF1A , Blu , ADAMTS9 , and DLEC1 were found in 60.22%, 80.65%, 62.37%, and 74.19%, respectively, in nasopharyngeal carcinoma tumors. A significant association between the methylation status of candidate genes with nasopharyngeal carcinoma was reported. The methylation of candidate genes significantly increased the risk of nasopharyngeal carcinoma in cancerous samples compared with control samples (OR > 1). Based on the value of the methylation index, methylation of at least one gene was found in 95.70% of nasopharyngeal tumors. Additionally, the methylation index among 93 tumors significantly correlated with advanced stage nasopharyngeal tumors., Conclusion: The study explored a higher frequency of hypermethylation at least one candidate gene. Methylation of a panel of potential genes can be utilized to discriminate between nasopharyngeal carcinoma and non-cancer cells, particularly in the advanced stages of nasopharyngeal carcinoma. Thus, it could serve as a valuable marker for the diagnosis and monitoring of nasopharyngeal carcinoma., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

DNA methylation, the most common epigenetic alteration, has been proven to play important roles in nasopharyngeal carcinoma (NPC). Numerous tumor suppressor genes located on the chromosome 3p, particularly in the region of 3p21, are frequently methylated in NPC, thus suggesting great potential for diagnosis of NPC. In this review, we summarize recent findings of tumor suppressor genes on chromosome 3 that likely drive nasopharyngeal tumor development and progression, based on previous studies related to the hypermethylation of these target genes. Better understanding will allow us to design further experiments to establish a potential test for diagnosis of NPC, as well as bring about methylated therapies to improve the treatment of NPC.

The genetic status of candidate tumor suppressor genes (TSGs) at chromosome 3p has not yet been elucidated in intrahepatic cholangiocarcinoma (iCCA). Herein, we retrospectively investigated 32 fresh iCCA case samples from a single medical institution to clarify mutations of 11 TSGs by next-generation sequencing. Validation of the mutations was performed on the MassARRAY platform or by high-resolution melting curve analysis. We then integrated the gene mutations into copy number alterations at chromosome 3p that had been generated in a previous study using the same fresh iCCA samples, and correlated the integration results with the clinicopathologic features. Nine of the 32 (28.1%) iCCA patients had gene mutations at chromosome 3p, totaling 11 mutations across five genes. Those included five (15.6%) BAP1 mutations, two each (6.3%) of CACNA2D3 and RASSF1 mutations, and one each (3.1%) of ATG7 and PLCD1 mutations. Six (18.8%) cases had concurrent loss of chromosome 3p and gene mutations. Patients with TSG mutations had shorter disease-free and survival times than those without the mutations. Our data showed that iCCA patients with TSG mutations at chromosome 3p faced an adverse prognosis. BAP1 was the common target of mutational inactivation and may be a principal driver of 3p21 losses. [ABSTRACT FROM AUTHOR]

Interstitial deletions of chromosome 3p14p12 are a rare chromosome rearrangement. Twenty-six patients have been reported in the literature to date, however, a specific clinical phenotype has not yet been delineated. We describe three patients (two new) with overlapping chromosome 3p14p12 deletions and review the clinical and molecular data of 11 well-characterized, published cases. These patients had a number of features in common, such as short stature, failure to thrive, facial dysmorphism, congenital heart defects, urogenital abnormalities, neurological problems, hearing loss, and global developmental delay, suggesting that the interstitial chromosome 3p14p12 deletion gives rise to a multiple congenital anomaly syndrome. Some of the patients show clinical overlap with other complex syndromes such as CHARGE syndrome. Genotype-phenotype analysis revealed candidate genes for parts of the clinical features suggesting that the 3p14 deletion is a contiguous gene syndrome. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The pathogenetic role, including its target genes, of the recurrent 3p12-p14 loss in cervical cancer has remained unclear. To determine the onset of the event during carcinogenesis, we used microarray techniques and found that the loss was the most frequent 3p event, occurring in 61% of 92 invasive carcinomas, in only 2% of 43 high-grade intraepithelial lesions ( CIN2/3), and in 33% of 6 CIN3 lesions adjacent to invasive carcinomas, suggesting a role in acquisition of invasiveness or early during the invasive phase. We performed an integrative DNA copy number and expression analysis of 77 invasive carcinomas, where all genes within the recurrent region were included. We selected eight genes, THOC7, PSMD6, SLC25A26, TMF1, RYBP, SHQ1, EBLN2, and GBE1, which were highly down-regulated in cases with loss, as confirmed at the protein level for RYBP and TMF1 by immunohistochemistry. The eight genes were subjected to network analysis based on the expression profiles, revealing interaction partners of proteins encoded by the genes that were coordinately regulated in tumours with loss. Several partners were shared among the eight genes, indicating crosstalk in their signalling. Gene ontology analysis showed enrichment of biological processes such as apoptosis, proliferation, and stress response in the network and suggested a relationship between down-regulation of the eight genes and activation of tumourigenic pathways. Survival analysis showed prognostic impact of the eight-gene signature that was confirmed in a validation cohort of 74 patients and was independent of clinical parameters. These results support the role of the eight candidate genes as targets of the 3p12-p14 loss in cervical cancer and suggest that the strong selection advantage of the loss during carcinogenesis might be caused by a synergetic effect of several tumourigenic processes controlled by these targets. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Pinpointing critical regions of recurrent loss may help localize tumor suppressor genes. To determine the regions of loss on chromosome 3p in neuroblastoma, we performed loss of heterozygosity analysis using 16 microsatellite markers in a series of 65 primary tumors and 29 neuroblastoma cell lines. In this study, we report the results and discuss the technical hurdles that we encountered during data generation and interpretation that are of relevance for current studies or tests employing microsatellites. To provide functional support for the implication of 3p tumor suppressor genes in this childhood malignancy, we performed a microcell-mediated chromosome 3 transfer in neuroblastoma cells. [ABSTRACT FROM AUTHOR]

Summary: CpG island methylator phenotype (CIMP) involving methylation abnormalities of tumor suppressor gene (TSG) on short arm of chromosome 3 (chromosome 3p) has not been so far epigenetically elucidated in non-small cell lung cancer (NSCLC). Using methylation-specific PCR (MSP) method, we examined methylation profiles for eight TSGs harbored in chromosome 3p in 60 NSCLC tissues and 60 paired normal tissues as well as 11 normal blood samples. CIMP positive is referred to having four or more than four synchronously methylated genes per sample. Consequently, 59 of 60 (98.3%) NSCLC presented promoter methylation of at least one gene while only one malignant tumor showed no methylation of any of eight genes. The frequency of promoter methylation for eight genes explored ranged from 12% for hMLH1 to 67% for RASSF1A given that of VHL (none) was not considered. Interestingly, CIMP+ was found in 56.7% (34/60) of NSCLC, and in 6.7% (4/60) of paired normal tissues and 0% (0/11) of normal blood samples, respectively; CIMP− was present in 43.3% (26/60) of NSCLC, 93.3% (56/60) of paired normal tissues, and 100% (11/11) of normal blood samples, respectively. The data suggest that CIMP status was significantly associated with NSCLC, paired normal tissues and normal blood samples (P <0.001). In addition, there appeared to be a significant association between CIMP status and survival prognosis of NSCLC (P =0.0166). In the present study, for the first time, we shed light on the presence of chromosome 3p-specific CIMP, which might play an important role in tumorigenesis of NSCLC. [Copyright &y& Elsevier]

Summary: Tunisia is one of the world’s intermediate risk areas for nasopharyngeal carcinoma (NPC). Loss of heterozygosity (LOH) on the short arm of chromosome 3 (3p) is the most frequent genetic change reported in NPC from endemic areas. In the present study, we investigate the incidence of LOH and microsatellite instability (MSI) on chromosome 3p in 49 microdissected primary NPC specimens and corresponding non-cancerous tissues from Tunisian patients using six microsatellite polymorphic markers. LOH at one or more markers was observed in 40 out of 48 informative cases (83.3%). The markers D3S1038 at 3p25.2–26.1 and D3S1076 at 3p21.1–21.2 have showed the highest frequency of LOH (51.3%), followed by D3S1067 at 3p14.3–21.1 (48.7%), D3S1568 at 3p21.3 (47.4%), D3S659 at 3p13 (15.3%), and D3S1228 at 3p14.1–14.2 (11%). Interestingly, MSI at one or more microsatellite markers was observed in 15 cases (31.2%). The highest frequency of MSI was presented by D3S1568 (18.4%), D3S1067 (17.9%), and D3S1038 (12.8%). With regard to clinicopathological features, LOH was found to be less common in young patients (under 25 years) than in adults (p =0.04), whereas MSI was found to be more frequent in patients under 45 years than in older patients (p =0.006). No significant correlation was found between LOH or MSI and the other clinicopathological features investigated including, gender, tumor size, lymph node metastasis, UICC clinical stage, and histological subtype. This study revealed different patterns of allelic imbalance on chromosome 3P in NPC between age groups in Tunisia, and suggests an alteration in the DNA mismatch repair machinery that may be, in part, responsible of the early age onset form of this disease in North African populations. More attention should be given to the mismatch repair system in the juvenile form of this disease in future studies. [Copyright &y& Elsevier]

Background: Although genetic abnormalities on 3p have been suggested to be linked to the development of squamous cell carcinoma of the head and neck, to the authors' knowledge no study to date has examined such genetic abnormalities in patients with squamous cell carcinoma of the tongue. In the current study, loss of heterozygosity (LOH) was evaluated at several loci within 3p, including the von Hippel-Lindau gene (VHL), in samples of tongue squamous cell carcinoma. In addition, the coding region of the intact VHL allele was screened for sequence mutations.Methods: DNA was extracted from tumor and nontumor tissues collected from 28 patients with tongue squamous cell carcinoma. LOH was investigated by analysis of single nucleotide polymorphisms within exon 3 of VHL and by microsatellite analysis within another 10 loci. Mutation analysis of the VHL gene was performed by polymerase chain reaction (PCR) amplification and sequencing of the coding region of the gene.Results: LOH within VHL was found at a high frequency (45.5%) within the tumor. However, mutations of the VHL gene were not detected in all tumor samples. LOH of other microsatellite markers on 3p was observed in 27.3% to 50% of tumor samples. Eleven (58%) of 19 samples that were informative at more than 2 loci exhibited LOH of at least 1 locus; 10 of these 11 cases exhibited LOH at multiple loci.Conclusions: A wide range of deletions in 3p, including at the VHL gene, may play a role in the development of tongue cancer. [ABSTRACT FROM AUTHOR]

Multiple chromosome 3p tumor suppressor genes (TSG) have been proposed in the pathogenesis of ovarian cancer based on complex patterns of 3p loss. To attain functional evidence in support of TSGs and identify candidate regions, we applied a chromosome transfer method involving cell fusions of the tumorigenic OV90 human ovarian cancer cell line, monoallelic for 3p and an irradiated mouse cell line containing a human chromosome 3 in order to derive OV90 hybrids containing normal 3p fragments. The resulting hybrids showed complete or incomplete suppression of tumorigenicity in nude mouse xenograft assays, and varied in their ability to form colonies in soft agarose and three-dimensional spheroids in a manner consistent with alteration of their in vivo tumorigenic phenotypes. Expression microarray analysis identified a set of common differentially expressed genes, such as SPARC, DAB2 and VEGF, some of which have been shown implicated in ovarian cancer. Genotyping assays revealed that they harbored normal 3p fragments, some of which overlapped candidate TSG regions (3p25–p26, 3p24 and 3p14-pcen) identified previously in loss of heterozygosity analyses of ovarian cancers. However, only the 3p12-pcen region was acquired in common by all hybrids where expression microarray analysis identified differentially expressed genes. The correlation of 3p12-pcen transfer and tumor suppression with a concerted re-programming of the cellular transcriptome suggest that the putative TSG may have affected key underlying events in ovarian cancer.Oncogene (2007) 26, 618–632. doi:10.1038/sj.onc.1209821; published online 7 August 2006 [ABSTRACT FROM AUTHOR]

We investigated the clinicopathological significance of aberrant methylation of the retinoic acid receptor-β2 (RARβ2), RAS association domain family 1A (RASSF1A) and fragile histidine triad (FHIT) genes located on choromosome 3p in 120 patients with primary non-small cell lung cancer (NSCLC) by a methylation-specific PCR method. Aberrant methylation of these was detected in 31 (26%), 35 (29%) and 43 (36%) tumors, respectively. There was no correlation with the methylation status of any of the genes. RARβ2 methylation was more frequently observed in patients with a smoking history (19 of 61, 31%) than in patients without one (3 of 29, 10%, P = 0.0373). RARβ2 methylation was also preferentially observed in advanced stage NSCLC (12 of 71 (17%) in stage I, 5 of 15 (33%) in stage II, 11 of 24 (46%) in stage III, and 3 of 8 (38%) in stage IV, P = 0.0057 (stage I versus II, III,and IV)). FHIT methylation was predominantly detected in tumors with vascular invasion (21 of 44, 48%, P = 0.0703) or lymphatic permeation (28 of 59, 47%, P = 0.0115). RASSF1A methylation was more frequently observed in adenocarcinomas (28 of 72, 39%) than in squamous cell carcinomas (6 of 45, 13%, P = 0.0033). These results indicate that aberrant methylation of the candidate tumor suppressor genes on 3p plays a respective role in the pathogenesis of NSCLC. [Copyright &y& Elsevier]

We performed allelotyping analysis at nine regions on chromosome 3p using 56 microdissected samples from 23 primary lung adenocarcinomas to examine the process of progression within individual lung adenocarcinoma with various grades of differentiation. Identical allelic patterns among various grades of differentiation were found in eight cases. Accumulation of allelic losses from high to lower differentiated portions was found in seven cases and accumulation of allelic losses from low to higher differentiated portions was found in five cases. Various allelic patterns among various grades of differentiation were found in three cases. These results suggested that allelic losses on 3p play an important role in morphological changes of lung adenocarcinomas. We also investigated the relationship between allelic losses on 3p and histological subtypes of lung adenocarcinoma. The frequencies of allelic losses at 3p14.2 and telomeric region of 3p21.3 were higher in papillary type tumour (nine out of 14, 64%and 11 out of 15, 73%) than in bronchioloalveolar carcinoma-type tumour (one out of 8, 13%; P=0.031 and four out of 12, 33%; P=0.057). These results indicated that allelic losses at 3p14.2 and telomeric region of 3p21.3 are related to pattern of the proliferation of lung adenocarcinoma.British Journal of Cancer (2004) 91, 1143-1148. doi:10.1038/sj.bjc.6602005 www.bjcancer.com Published online 3 August 2004 [ABSTRACT FROM AUTHOR]

3p deletions and telomerase reactivation are two of the most frequent events described in relation to non-small-cell lung cancer (NSCLC) pathogenesis. Moreover, a number of genes that map on 3p have been proposed as candidates to tumour-suppressor genes of importance in the lung cancer process. In this work, we analysed deletions at different 3p loci in relationship to telomerase activity in 66 NSCLCs obtained from patients who had suffered potentially curative surgery. Also, we evaluated prognostic implications. DNA samples were analysed for 3p deletions using five different polymorphic human dinucleotide repeat DNA markers (D3S1619 at 3p22.2, D3S3623 at 3p22.1, D3S1260 at 3p21.33, D3S3697 at 3p14.3, and D3S3722 at 3p21.2). Telomerase activity was investigated by a TRAP-based method. Possible correlations between the different molecular markers and distributions of disease-free survival were estimated. Our data revealed a significant correlation between telomerase activity and losses of heterozygosity (LOH) on D3S3697 (P=0.040), since all of the tumours showing deletion at this locus were positives for telomerase. Moreover, our results revealed clear associations with poor prognosis of patients, in the case of LOH at D3S1260 and D3S3697 (P=0.005 and 0.005, respectively). According to our data, potential repressors for telomerase may be located in chromosome 3p. [ABSTRACT FROM AUTHOR]

DNA methylation, the most common epigenetic alteration, has been proven to play important roles in nasopharyngeal carcinoma (NPC). Numerous tumor suppressor genes located on the chromosome 3p, particularly in the region of 3p21, are frequently methylated in NPC, thus suggesting great potential for diagnosis of NPC. In this review, we summarize recent findings of tumor suppressor genes on chromosome 3 that likely drive nasopharyngeal tumor development and progression, based on previous studies related to the hypermethylation of these target genes. Better understanding will allow us to design further experiments to establish a potential test for diagnosis of NPC, as well as bring about methylated therapies to improve the treatment of NPC. [ABSTRACT FROM AUTHOR]

Objective:To identify the molecular alterations found in 30 human papillomavirus (HPV) positive (n = 15) and negative (n = 15) vulvar carcinomas (VC) and their associated preinasive lesions (VIN [valvar intraepithelial neoplaisa]) and normal epithelium to determine a common molecular pathogenesis of HPV positive and negative VC.Methods:Loss of heterozygosity (LOH) at seven 3p chromosomal regions (3p12, 3p14.2, 2p14.3-21.1, 3p21.3, 3p22-24, 3p24.3, 3p25), 13p14 (RB) and 17p13.1 (p53) loci, and TP53 gene mutations in microdissected archival tissues were investigated.Results:Fourteen of fifteen HPV positive VC had HPN 16DNA sequences. The fractional regional loss index (FRL), an index of total allelic loss at all chromosomal regions analyzed, was greater in the HPV negative VCs than in the HPV positive tumors (FRL = 0.55 versus 0.32; P = .048) and was also greate in the HPV negative high-grade VINs as compared with the HPV positive lesions (0.29 versus 0.02; P = .002). Overall, LOH at any 3p region was frequent (80%) in both groups of cancer and in their associated VIN lesions. Although TP53 gene mutations were present in a minority of VCs (20%), allelic losses at the TP53 locus were ferquently present, especially in HPV negative VCs, as compared with the HPV positive tumors (62% versus 15%; P = .02).Conclusion:A greater number of molecular alterations are found in HPV negative VCs compred with HPV positive tumors. Allelic losses at 3p are common early events in vulvar carcinogenesis in HPV negative cancer detected at a high rate in the corresponding high-grade precursor lesions (VIN II/III). TP53 gene mutations with associated 17p13.1 LOH are more common in HPV negative cancers. [ABSTRACT FROM PUBLISHER]

The article presents a case study of a 38 year-old man with broad pink plaque on his back. It states that at the second request of the dermatopathologist, the man's original tumor was subjected to molecular assessment. It says that a gain in chromosome 11p was recognized after the completion of a comparative genomic hybridization (CGH). It notes that excellence in microscopical-molecular correlation will be prized if fiscal straits hinder the widening use of molecular techniques.

The author reflects on overdiagnosing of melanoma by diagnosticians. He presents several reasons on the tendency of diagnosticians to have many diagnoses, such as much confidence on their abilities and exact interpretation of their diagnostic criteria. He discusses several cases in which the phrase "in my opinion" is used in diagnosing, which is often used as a judgment or fact. The author advises to not make quick diagnosis for melanoma without thinking the consequences.

Background We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC) [odds ratio (OR)=1.2, 95% confidence interval (CI)=1.0-1.4, Ptrend=0.01] that showed a stronger association with the serous histological subtype (OR=1.3, 95% CI=1.1-1.5, Ptrend=0.003). Methods We sought to replicate this association in 12 other studies comprising 4,482 cases and 6,894 controls of white non-Hispanic ancestry in the Ovarian Cancer Association Consortium. Results No evidence for an association with all cancers or serous cancers was observed in a combined analysis of data from the replication studies (all: OR=1.0, 95% CI=0.9-1.1, Ptrend=0.61; serous: OR=1.0, 95% CI=0.9-1.1, Ptrend=0.85) or from the combined analysis of discovery and replication studies (all: OR=1.0, 95% CI=1.0-1.1, Ptrend= 0.28; serous: OR=1.1, 95% CI=1.0-1.2, Ptrend=0.11). There was no evidence for statistical heterogeneity in ORs across the studies. Conclusions Although rs2660753 is a strong a prostate cancer susceptibility polymorphism, the association with another hormonally related cancer, invasive EOC, is not supported by this replication study. Impact Our findings, based on a larger sample size, emphasize the importance of replicating potentially promising genetic risk associations.