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PubMed2026

Characteristics of fusion genes in breast cancer.

Fusion genes, arising from aberrant genomic rearrangements, represent critical oncogenic drivers with distinct oncogenic functions. Although relatively uncommon in breast cancer, accumulating evidence suggests that fusion genes contribute to tumor initiation, progression, and therapeutic resistance. This review first summarizes the molecular mechanisms underlying fusion gene formation, their frequency and subtype distribution, and advances in detection technologies in breast cancer. We then discuss how fusion genes reprogram oncogenic signaling pathways and mediate resistance to conventional and targeted therapies. Finally, we evaluate their translational potential as diagnostic biomarkers and therapeutic targets, emphasizing opportunities for precision oncology. By integrating current insights, this review underscores the multifaceted roles of fusion genes in breast cancer biology and highlights their promise for guiding the development of more effective, personalized treatment strategies.

Breast cancer↗
PubMed2005

Assay of Rab25 function in ovarian and breast cancers.

There is a multitude of critical steps during the pathogenesis of cancer that allow cells to acquire the ability to escape from normal controls on cell growth, to avoid programmed cell death, and to become malignant. Here, we describe a molecular approach that can be broadly applied to identify drivers of genomic aberrations in cancer development. In the process, areas of genomic aberrations and genes that are dysregulated by genomic amplification are identified by array comparative genomic hybridization (CGH) and transcription profiling, respectively, with major emphasis on coordinating amplification at the CGH and RNA level and on correlation with patient's outcomes. Once candidate genes are identified, we perform functional genomics by manipulating levels in normal and tumor cells using RNAi or transfection, and assessing a battery of cellular functions including proliferation, anti-apoptosis, loss of contact inhibition, changes in cell signaling or transcriptional profiles, anchorage-independent growth, and in vivo tumor growth. We have successfully used this approach to identify the RAB25 gene that has been implicated in the progression and aggressiveness of ovarian and breast cancers.

Apoptosis↗
PubMed1999

Diesel exhaust and lung cancer mortality in potash mining.

BACKGROUND: Findings from experimental studies on rodents and from epidemiological studies suggest that diesel exhaust may cause lung cancer. There is evidence that in several occupations, e.g., truck drivers and railway workers, the risk of lung cancer increases with duration of employment, and exposure to diesel exhaust provides the most likely explanation for these elevations of risk. METHODS: We investigated the association between lung cancer mortality and exposure to diesel exhaust in a cohort study. The cohort comprised 5, 536 male potash miners who were followed from 1970 to 1994. Exposure was assessed from concentration measurements of the total carbon (i. e., elemental and organic carbon in total) in personal dust samples. The concentration values were multiplied by years of exposure to give a quantitative exposure measure. The concentration levels ranged from 0.12 to 0.39 mg/m(3) total carbon in fine dust. Work histories and smoking habit data were obtained from medical company records. Causes of death were ascertained from death certificates. RESULTS: During the follow-up period, 424 deaths were recorded, including 133 of cancer, 38 of lung cancer. The relative risk of lung cancer between two groups with high and low exposure was 2.2 (95% confidence interval 0.8-6.0). With Cox regression, we found a lung cancer relative risk 1.7 (0.5-5.8) after twenty years of exposure. Extensive scrutiny proved smoking not to be a confounder in this study. CONCLUSIONS: The principal finding of the study is a doubling of relative lung cancer risk after twenty years of exposure in the workplaces with highest exposure. However, the observed elevation is nonsignificant even at a 90% level. Further follow-up is intended to enhance the study power.

Carbon↗
PubMed2026

Spatial Mapping of the Precancer-to-Cancer Transition in Breast and Prostate.

UNLABELLED: Breast and prostate cancers are both hormone-driven adenocarcinomas that undergo analogous invasion programs. Using lightsheet microscopy on intact tumors, we identified transitional junctions between precancerous and invasive regions. We then developed a multimodal serial-section workflow integrating volumetric reconstruction with spatial transcriptomics. Analysis of 319 spatial assays from 51 cases revealed gene expression features and novel structural insights defining the shift from precancer to invasive disease. In breast cancer, loss of MGP and PLAT was associated with invasive transition and promoted tumorigenesis in functional assays. In prostate cancer, GDF15, ALDH1A3, ANPEP, and FASN were upregulated along invasive progression, and their knockdown in PC-3 cells suppressed proliferation and migration. Enrichment of tumor-associated macrophages (SPP1+ and MS4A6A+) along non-triple-negative breast cancer breast cancer transitions highlights immune involvement as a potential driver of invasiveness. SIGNIFICANCE: Our method of defining precise spatial locations of invasive transition allows for the direct interrogation of transition drivers, presenting new therapeutic targets for the two most prevalent cancers and providing a framework for studying spatially defined mechanisms of tumor progression. See related commentary by Jing and Li, p. 1720.

Humans↗
PubMed1991

Mortality among professional drivers.

The mortality of truck drivers and taxi drivers was studied in Reykjavík. The national mortality rate was used for comparison, and the follow-up lasted until 1 December 1988. The 868 truck drivers (28,788.0 person-years) had an excess of lung cancer deaths [24 observed, 11.2 expected, standardized mortality ratio (SMR) 2.14], but fewer deaths than expected from respiratory diseases (15 observed versus 30.1 expected). The SMR from lung cancer did not steadily increase as the duration of employment increased, nor did it change with the length of follow-up. The SMR values did not deviate substantially from unity for the taxi drivers. Since the high mortality from lung cancer among the truck drivers did not seem to be due to their smoking habits, it might have been caused by one or more occupational factors, especially in light of this group's exposure to engine exhaust gases.

Cause of Death↗
PubMed2024

ERCC2 mutations alter the genomic distribution pattern of somatic mutations and are independently prognostic in bladder cancer.

Excision repair cross-complementation group 2 (ERCC2) encodes the DNA helicase xeroderma pigmentosum group D, which functions in transcription and nucleotide excision repair. Point mutations in ERCC2 are putative drivers in around 10% of bladder cancers (BLCAs) and a potential positive biomarker for cisplatin therapy response. Nevertheless, the prognostic significance directly attributed to ERCC2 mutations and its pathogenic role in genome instability remain poorly understood. We first demonstrated that mutant ERCC2 is an independent predictor of prognosis in BLCA. We then examined its impact on the somatic mutational landscape using a cohort of ERCC2 wild-type (n = 343) and mutant (n = 39) BLCA whole genomes. The genome-wide distribution of somatic mutations is significantly altered in ERCC2 mutants, including T[C>T]N enrichment, altered replication time correlations, and CTCF-cohesin binding site mutation hotspots. We leverage these alterations to develop a machine learning model for predicting pathogenic ERCC2 mutations, which may be useful to inform treatment of patients with BLCA.

Humans↗
PubMed2026

Cancer-associated fusion transcripts: mechanisms, functional roles, and clinical implications.

Fusion transcripts are hybrid RNA molecules generated through genomic rearrangements or RNA-level fusion mechanisms. They represent important molecular features of many cancers and can function as oncogenic drivers, diagnostic biomarkers, prognostic indicators, and therapeutic targets. Since the discovery of the BCR::ABL1 fusion in chronic myeloid leukemia, numerous cancer-associated fusion transcripts have been identified across hematologic malignancies and solid tumors. These fusion events encompass diverse biological mechanisms, including constitutively active kinases, aberrant transcription factors, epigenetic regulators, and non-coding fusion RNAs. This review summarizes current knowledge of the mechanisms underlying fusion transcript formation, including genomic rearrangement-dependent and rearrangement-independent processes, as well as fusion circular RNAs. The functional roles of fusion transcripts in cancer biology and their clinical relevance as diagnostic, prognostic, and predictive biomarkers are discussed. In addition, recent advances in fusion transcript detection and characterization are reviewed, including next-generation sequencing, long-read sequencing, single-cell approaches, artificial intelligence-assisted computational methods, and CRISPR/Cas9-mediated strategies for functional modeling and functional validation of fusion transcripts. Despite the rapid expansion of fusion transcript catalogs, the biological and clinical significance of most identified fusion events remains incompletely understood. Future progress will depend on integrating advanced sequencing technologies, artificial intelligence-assisted computational prioritization, and systematic functional validation to distinguish clinically actionable fusion transcripts from biologically neutral events. Such multidisciplinary approaches will be essential for translating fusion transcript research into precision oncology and improving cancer diagnosis, patient stratification, and targeted therapy.

Humans↗
PubMed1992

Occupational exposure of truck drivers to dust and polynuclear aromatic hydrocarbons: a pilot study in Geneva, Switzerland.

The exposure to dust and polynuclear aromatic hydrocarbons (PAH) of 15 truck drivers from Geneva, Switzerland, was measured. The drivers were divided between "long-distance" drivers and "local" drivers and between smokers and nonsmokers and were compared with a control group of 6 office workers who were also divided into smokers and nonsmokers. Dust was measured on 1 workday both by a direct-reading instrument and by sampling. The local drivers showed higher exposure to dust (0.3 mg/m3) and PAH than the long-distance drivers (0.1 mg/m3), who showed no difference with the control group. This observation may be due to the fact that the local drivers spend more time in more polluted areas, such as streets with heavy traffic and construction sites, than do the long-distance drivers. Smoking does not influence exposure to dust and PAH of professional truck drivers, as measured in this study, probably because the ventilation rate of the truck cabins is relatively high even during cold days (11-15 r/h). The distribution of dust concentrations was shown in some cases to be quite different from the expected log-normal distribution. The contribution of diesel exhaust to these exposures could not be estimated since no specific tracer was used. However, the relatively low level of dust exposure dose not support the hypothesis that present day levels of diesel exhaust particulates play a significant role in the excess occurrence of lung cancer observed in professional truck drivers.

Air Pollutants, Occupational↗
PubMed1997

Identification of genes with specific expression in pancreatic cancer by cDNA representational difference analysis.

cDNA representational difference analysis (cDNA-RDA) is a polymerase-chain-reaction-coupled subtractive and kinetic enrichment procedure for the isolation of differentially expressed genes. In this study, the technique was used to isolate novel genes specifically expressed in pancreatic cancer. cDNA-RDA was done on cDNA reverse transcribed from a poly(A)+ mRNA pool made from 10 cancer tissues (tester) by using as a driver a cDNA from a poly(A)+ mRNA pool made from a combination of 10 tissues of chronic pancreatitis and 10 healthy pancreatic tissues. The use of chronic pancreatitis in addition to healthy pancreas mRNA in the driver preparation eliminated the influence of stromal tissue components present as contamination in the cancer-specific preparations. Such cDNA-RDA led to the isolation of 16 distinct, cancer-specific gene fragments. These were confirmed to be overexpressed in pancreatic cancer tissues by Northern blot analysis. Sequence analysis revealed homologies to five genes previously implicated in the carcinogenesis of the pancreas or other tissues. Eleven fragments had no significant homology to any known gene and thus represent novel candidate disease genes. The experiments demonstrate that cDNA-RDA is a reproducible and highly efficient method for the identification of novel genes with cancer-specific expression.

Annexin A3↗
PubMed2004

Austin Bowel Cancer Consortium: changing culture in bowel cancer care.

The Austin Bowel Cancer Consortium aimed to identify drivers of clinical decision-making so as to inform a continuous practice improvement approach to the use of evidence. Strategies for engaging clinicians included a direct clinician-clinician approach, gaining the support of opinion leaders and using the clinicians' desire for patient outcome data. Interviews with clinicians identified barriers to using evidence in practice. These included poor integration of medical and surgical disciplines, different learning styles, negative attitudes to guidelines and pathways, and no consensus as to what is an effective multidisciplinary team. A clinical implementation group provided a forum for interaction between disciplines. The group agreed on management pathways covering the continuum of care and developed decision-support software for use in the clinic. Interviews with patients and carers highlighted psychosocial and communication difficulties and prompted greater clinician awareness. Consumers developed patient information resources with minimal assistance from project staff. The clinical encounter is the prime site for change for putting evidence into practice, rather than trying to change individual clinicians.

Attitude of Health Personnel↗
PubMed2026

Feasibility of routine clinical liquid-based cytology for lung cancer compact panel testing.

BACKGROUND: The Lung Cancer Compact Panel (cPANEL) is a recently approved highly sensitive multiplex gene panel in Japan that supports both DNA- and RNA-based next-generation sequencing. Although cytological specimens are acceptable for cPANEL, unfixed cell pellets or dedicated preservation tubes are typically recommended. However, evidence remains limited regarding whether residual liquid-based cytology (LBC) cell suspensions prepared for routine cytological diagnosis can be used directly for cPANEL testing without dedicated molecular preservation or additional preanalytical processing. In this study, we evaluated the feasibility of applying LBC specimens that are widely used in contemporary clinical practice to cPANEL. METHODS: We analyzed DNA and RNA quality in 69 clinical LBC specimens. Among these, 51 specimens containing non-small cell lung cancer cells with previously determined driver alteration status were subjected to cPANEL testing to evaluate assay concordance with clinical companion diagnostic results. RESULTS: DNA integrity was generally well preserved (DNA Integrity Number [DIN]: 6.2 ± 1.5). In contrast, RNA integrity showed greater variability (DV200: 16.4 ± 12.1%). ThinPrep-fixed specimens demonstrated lower DIN and DV200 values compared with CytoRich Red-fixed specimens. Although all samples successfully passed the DNA-based cPANEL assay, six cases (11.8%) failed the RNA-based assay, with RNA yield being a major contributing factor. Among the 46 evaluable specimens, concordance was 95.7% and sensitivity was 92.3%, or 88.9% including RNA module failures as cPANEL-negative. CONCLUSIONS: With appropriate fixative selection and adequate cellularity, cPANEL using clinical LBC specimens may serve as a practical diagnostic platform. We demonstrated that routine LBC specimens can be directly applied to cPANEL without special preanalytical processing.

Humans↗
PubMed2003

Cost-effectiveness of defunctioning stomas in low anterior resections for rectal cancer: a call for benchmarking.

HYPOTHESIS: Anastomotic leakage is the most important cost driver in patients who undergo low anterior resection (LAR) for rectal cancer. Creating defunctioning stomas to protect colorectal anastomoses may also have a major effect on the overall costs. Unselected creation of defunctioning stomas in most of these patients may be associated with higher overall costs compared with a program that has a low rate of defunctioning stomas and an acceptable anastomotic leakage rate. DESIGN: Cost-effectiveness analysis. SETTING: Secondary referral center. PATIENTS: Performing a cost analysis from the viewpoint of a hospital provider, we reviewed data of 70 consecutive patients who underwent LARs with (n = 19) or without (n = 51) a defunctioning colostomy. A scenario analysis was performed using data derived from the medical literature to assess a plausible range of leakage and stoma rates. MAIN OUTCOME MEASURE: Costs per treatment option and incremental cost-effectiveness ratio according to various treatment scenarios. RESULTS: Performing an LAR without a stoma and no anastomotic leakage is associated with significantly lowest costs (8.400 euro; P<.001) compared with patients with a stoma (13.985 euro) and patients with anastomotic leakage (42.250 euro). The most important cost drivers were anastomotic leakages and defunctioning stomas. A leakage rate of 16.5% in patients without a stoma would be necessary to balance the overall costs of patients with stomas. The incremental cost-effectiveness ratio would be 158.705 euro and 60.915 euro per leak, respectively, avoided in patients with defunctioning stomas assuming a leakage rate lower than 3% and 6%, respectively, in patients who did not undergo a colostomy. A 1-way sensitivity analysis revealed that duration and costs of intensive care unit care were the only factors that may considerably alter our results. CONCLUSIONS: A suggested benchmark for an LAR should be a rate of 10% or less for defunctioning stomas and anastomatic leaks; that would limit the overall costs to 12,000 euro per patient treated. Against the background of a lack of universally valid criteria for the creation of defunctioning stomas, our aim should be to reduce the rate of defunctioning stomas because of their major effect on the overall costs especially in programs with a lower leakage rate. Higher leakage rates despite higher stoma rates depend more on the skill of the surgeon than on the characteristics of the patient and higher leakage should lead to a change in surgical technique strategy.

Aged↗
PubMed2005

The epidemiology of breast cancer in Maori women in Aotearoa New Zealand: implications for screening and treatment.

AIM: To describe the epidemiology of breast cancer in Maori and non-Maori women in New Zealand, and to identify the implications for breast cancer screening and treatment policy and practice. METHODS: New Zealand Census Mortality Study (NZCMS)-adjusted age-specific incidence and mortality rates for breast cancer in total and sole Maori and non-Maori women were calculated using registration and mortality data obtained from New Zealand Health Information Service for 1996-2000. RESULTS: Despite similar age-specific incidence rates of breast cancer in total Maori and non-Maori women under 50 years of age, total Maori women aged 25-59 years had higher age-specific mortality from breast cancer than non-Maori. A similar pattern is seen for sole Maori age-specific rates; however, the rates are even higher than total Maori rates. DISCUSSION: Possible drivers of ethnic disparities in breast cancer mortality require investigation--particularly the role of access to breast cancer screening and treatment for Maori women compared to non-Maori. Specific initiatives are continually needed to ensure that Maori women are able to access breast cancer screening--otherwise ethnic inequalities in mortality will persist. The interaction between deprivation and ethnicity in breast cancer incidence and mortality analyses should be investigated in future analyses.

Adult↗
PubMed1992

Impact of a community health promotion program on existing organizations: the Minnesota Heart Health Program.

A community organization strategy was used in the delivery of health education programs by the Minnesota Heart Health Program (MHHP). The effectiveness of the approach was evaluated to determine whether an enhanced health promotion delivery system had developed in MHHP communities by the end of the intervention period or whether the intervention had suppressed community efforts. 'Social connectedness' among providers, as measured by health promotion network size, also was expected to be higher in intervention communities. Six Midwestern communities were studied: the MHHP communities of Mankato, MN and Fargo, ND--Moorhead, MN with two matched comparison communities for each (Winona, MN, St Cloud, MN and Eau Claire, WI, Sioux Falls, SD). Nine areas of health promotion were assessed, including the five heart disease risk factor areas where education campaigns had been implemented (smoking cessation, weight loss, eating patterns, exercise, and heart disease education and screening) and four other areas where community programs are common (chemical dependency; home, personal and drivers' safety; stress management; and cancer education and screening). Indicators of the health promotion delivery system were developed (program options and program participation), and data were collected in separate surveys of 438 community organization providers and 320 larger worksites in the six communities. Results showed no suppression of health promotion delivery systems in MHHP communities. Instead, the survey of larger worksites showed that there was greater participation in heart disease health promotion and greater 'social connectedness' among worksites in both intervention communities. Also, there were more heart disease health promotion programs in the larger intervention community of Fargo-Moorhead. In the community organization survey, results favored the larger intervention community over its comparison communities in heart disease health promotion program options and in 'social connectedness' but not in program participation. However, survey results favored one of the comparison communities (Winona) over the smaller intervention community (Mankato) on all indicators in this survey. The greater impact of the MHHP intervention at worksites suggests that institutionalization may be more likely in stable organizations whose current needs and interests fit the goals of the intervention activity.

Adult↗
PubMed1985

Professional driving, smoking, and lung cancer: a case referent study.

In a case referent study of about 600 cases of male lung cancer in northern Sweden the risk in professional drivers was specifically studied. Data concerning occupations, time and type of employment, and smoking habits were collected by questionnaires directed to close relatives. On average, professional drivers were heavier smokers and this was the chief cause of a slightly increased crude risk ratio in the study as a whole. Smoking drivers in an upper age group (70 and over) had a high relative risk of lung cancer, whereas in a lower age group (under 70) no significant increase was found. The relative risk in non-smoking drivers in the upper age group was moderately raised with borderline statistical significance. The high relative risk estimated for smoking drivers in the upper age group suggests a synergistic effect between smoking and occupational exposure.

Adult↗
PubMed2006

Overexpression of the wip1 gene abrogates the p38 MAPK/p53/Wip1 pathway and silences p16 expression in human breast cancers.

Wild-type p53-induced phosphatase (Wip1 or PPM1D) is a serine/threonine protein phosphatase expressed under various stress conditions, which selectively inactivates p38 MAPK. The finding that this gene is amplified in association with frequent gain of 17q21-24 in breast cancers supports its role as a driver oncogene. However, the pathogenetic mechanism of the wip1 gene expression in breast carcinogenesis remains to be elucidated. In this study, we examine Wip1 mRNA and protein expression in 20 breast cancer tissues and six cell lines. We additionally investigate the relationship among Wip1, active p38 MAPK, p53, and p16 proteins. In our experiments, Wip1 mRNA was significantly upregulated in 7 of 20 (35%) invasive breast cancer samples. Overexpression of Wip1 was inversely correlated with that of active (phosphor-) p38 MAPK (P = 0.007). Furthermore, Wip1-overexpressing tumors exhibited no or low levels of p16, which normally accumulates upon p38 MAPK activation (P = 0.057). Loss of p16 expression was not associated with hypermethylation of its promoter or loss of heterozygosity on 9p21. Among the 135 primary breast carcinomas further examined, a significant association was found between the Wip1 overexpression and negative staining for p53 (P value = 0.057), indicating that the tumors are wild-type for p53. This is first report showing that Wip1 overexpression abrogates the homeostatic balance maintained through the p38-p53-Wip1 pathway, and contributes to malignant progression by inactivating wild-type p53 and p38 MAPK as well as decreasing p16 protein levels in human breast tissues.

Biomarkers, Tumor↗
PubMed2026

DBP-CanPred: a machine learning model for predicting cancer-causing mutations in DNA-binding proteins.

INTRODUCTION: The fundamental cellular processes, including transcriptional regulation, chromatin organization, and genome maintenance, are regulated by DNA-binding proteins (DBPs). Mutations in DBPs can alter protein-DNA interactions, leading to tumor development. However, identifying such driver mutations remains a major challenge due to limitations of experimental approaches. METHODS: We have trained a machine learning model, DBP-CanPred, to identify driver mutations in DBPs. We used the sequence-derived evolutionary features, as well as structure-based features such as mutation-perturbed structural descriptors. RESULTS: We evaluated DBP-CanPred using a curated test set, achieving an AU-ROC of 0.86 and a balanced accuracy of 0.79. Further analysis based on substitution-type showed consistent performance across different categories, especially higher performance on charged residues. In addition, we applied the model on an independent dataset and identified potential driver mutations with high confidence scores. DISCUSSION: The study contributes to understanding mutation patterns in DNA-binding proteins and supports variant interpretation in cancer research.

DNA-binding proteins↗
PubMedDate not supplied

Occupation and the risk of lung cancer by histologic types and morphologic distribution: a case control study in Turkey.

BACKGROUND: The lung cancer incidence rate in Turkey has been increasing since the early 1980's. Etiology of lung cancer could be affected by differences in lifestyle, working conditions, and occupational exposures. OBJECTIVES: A hospital based case-control study was conducted in Turkey to provide information on the role that occupation plays in lung cancer etiology and the relationship between occupations and histologic types and the morphologic distribution of lung cancer. METHODS: A total of 1,354 male cases and 1,519 controls were analysed. Basic information was obtained from patients from a standardised questionnaire. Occupational titles of the subjects were classified by standard occupational and industrial codes. Age- and smoking-adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: Excess lung cancer occurred among fire-fighters (OR: 6.8, CI: 1.3-37.4), drivers (OR: 1.4, CI: 1.1-2.0), textile workers (OR: 1.7, CI: 1.1-2.7), water treatment plant workers (OR: 2.2, CI: 1.1-4.3) and highway construction workers (OR: 1.5, CI: 1.0-2.5). Workers in the textile and grain milling industries were shown to have a significant excess risk of squamous cell carcinoma. Textile workers, and those working at water treatment plants had excess risk of small cell carcinoma. Construction workers had excess risk of adenocarcinoma. Fire-fighters and workers at textile plants, grain mills, water treatment plants, and in steel production were exposed to a high risk of peripheral tumors while the risk of central tumors was excessive among drivers and highway construction workers. CONCLUSIONS: The risk of lung cancer was associated with several occupations and peripheral located tumors and squamous lung cancer was the most common type.

Adenocarcinoma↗