| 1. |
- 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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| 2. |
- Hansen, S, et al.
(författare)
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Microvessel density compared with the Chalkley count in a prognostic study of angiogenesis in breast cancer patients
- 2004
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 44:5, s. 428-436
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Evaluation of angiogenesis by intratumoral vessel profiles can be performed by different methods. The aim of this study was to investigate the prognostic value of estimates obtained by the intratumoral microvessel density (MVD) method and then to compare with corresponding estimates obtained by the Chalkley method. Methods and Results: A total of 330 patients treated for primary, unilateral, invasive breast carcinoma were included. The median follow-up time was 14 years and 4 months. The microvessels were immunohistochemically stained by antibodies to CD34. MVD was not significantly correlated with any clinicopathological variables. By univariate analysis, MVD showed no prognostic value with regard to recurrence-free survival (RFS) or overall survival (OS), while the Chalkley count had significant prognostic value (P < 0.0001; RFS and OS). In the Cox multivariate analysis, MVD had no prognostic impact {median HR [confidence interval (CI)] was 0.93 [0.66, 1.32] for RFS; and HR [CI] was 0.86 [0.62, 1.19] for OS}, while the Chalkley count [median HR (CI) was 2.12 (1.48, 3.06) for RFS; and HR (CI) was 1.71 (1.23, 2.37) for OS] provided independent prognostic value when adjusted for age, menopausal status, axillary lymph node status, tumour size, histological grade, adjuvant systemic treatment and radiation therapy. In comparing the results obtained by MVD in our study with those from other published studies we find good agreement. Conclusions: The Chalkley count technique seems to be preferable for estimating angiogenesis with regard to the prognostic stratification of breast cancer patients, based on its strong prognostic impact, and acceptable reproducibility.
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