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Multiregion whole-exome sequencing uncovers the genetic evolution and mutational heterogeneity of early-stage metastatic melanoma

Cancer genome sequencing has shed light on the underlying genetic aberrations that drive tumorigenesis. However, current sequencing-based strategies, which focus on a single tumor biopsy, fail to take into account intratumoral heterogeneity. To address this challenge and elucidate the evolutionary history of melanoma, we performed whole-exome and transcriptome sequencing of 41 multiple melanoma bi

Metastasis stimulation by hypoxia and acidosis-induced extracellular lipid uptake is mediated by proteoglycan-dependent endocytosis

Hypoxia and acidosis are inherent stress factors of the tumor microenvironment and have been linked to increased tumor aggressiveness and treatment resistance. Molecules involved in the adaptive mechanisms that drive stress-induced disease progression constitute interesting candidates of therapeutic intervention. Here, we provide evidence of a novel role of heparan sulfate proteoglycans (HSPG) in

Monarchies as corporate brands

This paper explores monarchies through a corporate branding lens. It is based on extensive field interviewing of individuals with knowledge and experience in what we (not they) term “managing the Crown as a brand,” including senior members of the Swedish Royal Court and the Swedish Royal Family. It also draws from literature regarding monarchies across a range of disciplines beyond management; we

Sons of men with prostate cancer : their attitudes regarding possible inheritance of prostate cancer, screening, and genetic testing

OBJECTIVES: To study attitudes regarding possible inheritance of prostate cancer among sons of men with prostate cancer.METHODS: A questionnaire was sent to 69 men with prostate cancer and their 101 unaffected sons. All participants were also interviewed by telephone. Sociodemographic data were collected, as were data about the fathers' disease.RESULTS: The response rate was high; 100 sons (99%) a

Transcription of human endogenous retroviral sequences related to mouse mammary tumor virus in human breast and placenta : similar pattern in most malignant and nonmalignant breast tissues

The human genome contains a large variety of sequences related to the mouse mammary tumor virus (MMTV). We have investigated the range of expression of human endogenous retroviral sequences (HERVs) related to MMTV (human MMTV-like; HML) as RNA in 60 breast cancers, 8 nonmalignant breast tissues, and 9 placentas. This was monitored using HML group-specific oligonucleotide probes in hybridizations t

Distinct somatic genetic changes associated with tumor progression in carriers of BRCA1 and BRCA2 germ-line mutations

BRCA1 and BRCA2 mutations confer increased risk for development of breast cancer, but a number of additional, currently largely unknown, somatic genetic defects must also accumulate in the breast epithelial cells before malignancy develops. To evaluate the nature of these additional somatic genetic defects, we performed a genome-wide survey by comparative genomic hybridization on breast cancers fr

Tumour biological features of BRCA1-induced breast and ovarian cancer

BRCA1 mutations, although implicated in disease predisposition in a major part of the hereditary breast cancer population, do not seem to be crucially involved in tumorigenesis of sporadic breast and ovarian cancers. This suggests that tumours arising in BRCA1 mutation carriers may differ from BRCA1 negative hereditary and sporadic cancer in genetic and biological features, as well as in clinical

Cutaneous malignant melanoma in southern Sweden 1965, 1975, and 1985. Prognostic factors and histologic correlations

BACKGROUND: There is a worldwide increase in the incidence of cutaneous malignant melanoma (CMM) among whites. In Sweden, a five-fold increase has been recorded since 1960, although the increase in mortality rate is substantially lower. Tumor thickness is recognized as the most important histologic prognostic factor for primary melanoma. In a previous study, the authors did not find any significan

A segregation analysis of testicular cancer based on Norwegian and Swedish families

Clustering of testicular cancer cases in families is well known, although the aetiology is not. We present the results of a segregation analysis performed with the algorithm Pointer on familial data on 978 Scandinavian patients with testicular cancer. The segregation analysis favoured the involvement of major gene effects over models incorporating solely polygenic effects in testicular cancer aeti

Allelic loss at chromosome 13q12-q13 is associated with poor prognosis in familial and sporadic breast cancer

Loss of heterozygosity (LOH) was analysed in 84 primary tumours from sporadic, familial and hereditary breast cancer using five microsatellite markers spanning the chromosomal region 13q12-q13 which harbours the BRCA2 breast cancer susceptibility gene, and using one other marker located within the RBI tumour-suppressor gene at 13q14. LOH at the BRCA2 region was found in 34% and at RBI in 27% of th

Overall cancer incidence not increased after prosthetic knee replacement : 14,551 patients followed for 66,622 person-years

It is unknown whether patients as a consequence of prosthetic joint replacement are at a higher risk of developing cancer. We therefore analyzed cancer incidence following prosthetic knee replacement (TKR). The observed cancer incidence in 14,551 patients from the population-based Swedish Knee Arthroplasty Register who have undergone TKR because of osteoarthrosis (OA, n = 10,120) or rheumatoid art

A novel p53 germline alteration identified in a late onset breast cancer kindred

Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer. Most mutations found are of missense type and located in the central region of the gene (exons 5 to 8). In the present study, a germline p53 alteration was

Novel germline p16 mutation in familial malignant melanoma in southern Sweden

The p16 (CDKN2/MTS1/INK4a) malignant melanoma susceptibility gene was analyzed in 10 melanoma kindreds from southern Sweden using single-stranded conformation polymorphism analysis of all three exons and flanking intron regions followed by sequence analysis. A novel germline mutation, constituting an in-frame 3-bp duplication at nucleotide 332 in exon 2, was identified in two families (Lund M2 and

Blood transfusion as a risk factor for non-Hodgkin lymphoma

In a case-control study of 280 out of 426 consecutive patients with a recent diagnosis of non-Hodgkin lymphoma (NHL) and 1827 control subjects, 53 (19%) and 230 (13%) respectively had received blood transfusions 1 year or more before the interview. Using an age- and sex-stratified analysis the odds ratio (OR) for transfusion was 1.74 (95% CI 1.24-2.44). ORs were also determined for transfusions re

Risk of malignant melanoma in relation to drug intake, alcohol, smoking and hormonal factors

In a population-based, matched case-control study from southern Sweden of 400 patients with a first diagnosis of malignant melanoma and 640 healthy control subjects aged 15-75 years, the association between commonly prescribed drugs, alcohol, smoking and malignant melanoma was evaluated. In addition, the relation between reproductive and hormonal factors and melanoma in women was studied. It was f

Correlation between karyotypic pattern and clincopathologic features in 125 breast cancer cases

A correlation analysis was performed on 125 cytogenetically characterized breast cancer cases to assess the relationship between the tumor karyotype and clinicopathologic features. The carcinomas of young women had a higher modal chromosome number than those of older women. The number of chromosomal aberrations and modal chromosome number were also found to correlate with the histologic type, grad

Reproducibility of a self-administered questionnaire for assessment of melanoma risk

BACKGROUND: The reproducibility of a self-administered questionnaire on different epidemiological variables was examined in a random sample of a cohort of healthy women from the South Swedish Health Care Region. An identical questionnaire has previously been used for assessment of melanoma risk, in a population-based, matched, case-control study from the same region.METHODS: Repeat questionnaires

Risk of cancer in relatives of testicular cancer patients

The incidence of cancer at sites other than the testis has been investigated in the families of 797 Norwegian and 178 Swedish patients diagnosed with testicular cancer during 1981-91. In the families of the Norwegian patients, the total number of cancers in the relatives was significantly lower than the expected number derived from national incidence rates [observed number of cancers 250, expected

Familial testicular cancer in Norway and southern Sweden

Information about occurrence of testicular cancer (TC) in relatives of TC patients has been collected using questionnaires from 797 out of 922 consecutive Norwegian and 178 out of 237 Swedish patients with TC seen at the Norwegian Radium Hospital and the University Hospital Lund in Sweden during 1981-91. Fifty-one Norwegian and five Swedish patients had a relative with confirmed TC. Thus, 51/922 (