A simple qualitative approach for mapping regional landslide susceptibility in the Faroe Islands

The Faroe Islands in the North Atlantic Ocean are highly susceptible to landslides. Following recent landslide incidents, Jarðfeingi (Faroese Earth and Energy Directorate) has pointed out, that the risk of human lives or of property being lost or affected by landslides may be increasing. This paper aims at presenting and testing a simple qualitative approach for mapping regional landslide susceptibility in the Faroe Islands, using few key parameters. The susceptibility model holds information about both landslide initiation areas and runout zones. Landslide initiation areas are determined from slope angle thresholds (25°–40°) and soil cover data, while runout zones are delineated using the angle of reach approach taking into account the presence/absence of geological benches in the runout path, which has not been considered in earlier studies. Data input is obtained from a landslide database containing 67 debris flows throughout the Faroe Islands. Angle of reach values differ significantly with the presence/absence of geological benches in the runout path. Two values of angle of reach, 21.5° and 27.6°, are used for calculating runout zones. The landslide susceptibility model is tested in a study area at the town of Klaksvík in the northern part of the Faroe Islands. A map validation comparing predicted susceptibility zones with a validation-dataset of 87 actual landslides in the study area reveal that 69% and 92%, respectively, of actual landslide initiation areas and runout zones are correctly predicted. Moreover 87% of the actual landslides are included in the overall predicted landslide susceptibility areas

Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each step. Our data, contrary to the proposed model of early dissemination of metastatic cells and parallel progression of primary tumors and metastases, provide evidence of linear progression of breast cancer with relatively late dissemination from the primary tumor. The genomic discordance between the different stages of tumor evolution in this patient emphasizes the importance of molecular profiling of metastatic tissue directing molecularly targeted therapy at recurrence

Genomic Analyses of Breast Cancer Progression Reveal Distinct Routes of Metastasis Emergence

A main controversy in cancer research is whether metastatic abilities are present in the most advanced clone of the primary tumor or result from independently acquired aberrations in early disseminated cancer cells as suggested by the linear and the parallel progression models, respectively. The genetic concordance between different steps of malignant progression is mostly unexplored as very few studies have included cancer samples separated by both space and time. We applied whole exome sequencing and targeted deep sequencing to 26 successive samples from six patients with metastatic estrogen receptor (ER)-positive breast cancer. Our data provide support for both linear and parallel progression towards metastasis. We report for the first time evidence of metastasis-to-metastasis seeding in breast cancer. Our results point to three distinct routes of metastasis emergence. This may have profound clinical implications and provides substantial novel molecular insights into the timing and mutational evolution of breast cancer metastasis

Development of a Precision Medicine Workflow in Hematological Cancers, Aalborg University Hospital, Denmark

Within recent years, many precision cancer medicine initiatives have been developed. Most of these have focused on solid cancers, while the potential of precision medicine for patients with hematological malignancies, especially in the relapse situation, are less elucidated. Here, we present a demographic unbiased and observational prospective study at Aalborg University Hospital Denmark, referral site for 10% of the Danish population. We developed a hematological precision medicine workflow based on sequencing analysis of whole exome tumor DNA and RNA. All steps involved are outlined in detail, illustrating how the developed workflow can provide relevant molecular information to multidisciplinary teams. A group of 174 hematological patients with progressive disease or relapse was included in a non-interventional and population-based study, of which 92 patient samples were sequenced. Based on analysis of small nucleotide variants, copy number variants, and fusion transcripts, we found variants with potential and strong clinical relevance in 62% and 9.5% of the patients, respectively. The most frequently mutated genes in individual disease entities were in concordance with previous studies. We did not find tumor mutational burden or micro satellite instability to be informative in our hematologic patient cohort