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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 6. |
- Stenman, UH, et al.
(författare)
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Prognostic value of serum markers for prostate cancer
- 2005
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 39:216, s. 64-81
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of prostate cancer has increased dramatically during the last 10-15 years and it is now the commonest cancer in males in developed countries. The increase is mainly caused by the increasing use of opportunistic screening or case-finding based on the use of prostate-specific antigen (PSA) testing in serum. With this approach, prostate cancer is detected 5-10 years before giving rise to symptoms and on average 17 years before causing the death of the patient. While this has led to detection of prostate cancer at a potentially curable stage, it has also led to substantial overdiagnosis, i.e. detection of cancers that would not surface clinically in the absence of screening. A major challenge is thus to identify the cases that need to be treated while avoiding diagnosing patients who will not benefit from being diagnosed and who will only suffer from the stigma of being a cancer patient. It would be useful to have prognostic markers that could predict which patients need to be diagnosed and which do not. Ideally, it should be possible to measure these markers using non-invasive techniques, i.e. by means of serum or urine tests. As it is very useful for both early diagnosis and monitoring of prostate cancer, PSA is considered the most valuable marker available for any tumor. Although the prognostic value of PSA is limited, measurement of the proportion of free PSA has improved the identification of patients with aggressive disease. Furthermore, the rate of increase in serum PSA reflects tumor growth rate and prognosis but, due to substantial physiological variation in serum PSA, reliable estimation of the rate of PSA increase requires follow-up for at least 2 years. Algorithms based on the combined use of free and total PSA and prostate volume in logistic regression and neural networks can improve the diagnostic accuracy for prostate cancer, and assays for minor subfractions of PSA and other new markers may provide additional prognostic information. Markers of neuroendocrine differentiation are useful for the monitoring of androgen-independent disease and various bone markers are useful in patients with metastatic disease.
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