The Norwegian childhood cancer biobank

Background - The rapidly expanding era of “omics” research is highly dependent on the availability of quality-proven biological material, especially for rare conditions such as pediatric malignancies. Professional biobanks provide such material, focusing on standardized collection and handling procedures, distinctive quality measurements, traceability of storage conditions, and accessibility. For pediatric malignancies, traditional tumor biobanking is challenging due to the rareness and limited amount of tissue and blood samples. The higher molecular heterogeneity, lower mutation rates, and unique genomic landscapes, however, renders biobanking of this tissue even more crucial. Aim - The aim of this study was to test and establish methods for a prospective and centralized biobank for infants, children, and adolescents up to 18 years of age diagnosed with cancer in Norway. Methods - Obtain judicial and ethical approvals and administration through a consortium, steering committee, and advisory board. Develop pipelines including SOPs for all aspects in the biobank process, including collection, processing and storing of samples and data, as well of quality controlling, safeguarding, distributing, and transport. Results - The childhood cancer biobanking started at Oslo University Hospital in March 2017 and was from 2019 run as a national Norwegian Childhood Cancer Biobank. Informed consent and biological samples are collected regionally and stored centrally. Approximately 12 000 samples from 510 patients and have been included by January 1, 2021, representing a 96% consent and participation rate among our newly diagnosed patients. Conclusion - A well-functioning nationwide collection and centralized biobank with standardized procedures and national storage for pediatric malignancies has been established with a high acceptance among families

Genomic evolution of breast cancer metastasis and relapse

A.G.L. and J.H.R.F. were supported by a Cancer Research UK Program Grant to Simon Tavaré (C14303/A17197).Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancer genes than early drivers. These include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.Publisher PDFPeer reviewe

Subclonal diversification of primary breast cancer revealed by multiregion sequencing.

The sequencing of cancer genomes may enable tailoring of therapeutics to the underlying biological abnormalities driving a particular patient's tumor. However, sequencing-based strategies rely heavily on representative sampling of tumors. To understand the subclonal structure of primary breast cancer, we applied whole-genome and targeted sequencing to multiple samples from each of 50 patients' tumors (303 samples in total). The extent of subclonal diversification varied among cases and followed spatial patterns. No strict temporal order was evident, with point mutations and rearrangements affecting the most common breast cancer genes, including PIK3CA, TP53, PTEN, BRCA2 and MYC, occurring early in some tumors and late in others. In 13 out of 50 cancers, potentially targetable mutations were subclonal. Landmarks of disease progression, such as resistance to chemotherapy and the acquisition of invasive or metastatic potential, arose within detectable subclones of antecedent lesions. These findings highlight the importance of including analyses of subclonal structure and tumor evolution in clinical trials of primary breast cancer

Bruk av standardiserte besvarelser i patologi - et kvalitetsforbedrende tiltak

Fullstendige og korrekte patologirapporter er viktige for å kunne gi kreftomsorg med god kvalitet. Kreftregisteret og Den norske patologforening har tidligere utviklet en nasjonal elektronisk mal for rapportering av operasjonspreparater med colorectal cancer. Prosjektet ble satt i verk for å undersøke 1) om kvalitetsrutiner i norske patologilaboratorier påvirker hvor fullstendige rapportene er utfylt og 2) om den nasjonale elektroniske malen bedrer rapporteringen sammenlignet med andre måter å formidle resultatene på. Et spørreskjema om kvalitetsrutiner ble sendt til alle landets 21 patologilaboratorier. Alle patologirapporter mottatt Kreftregisteret i en 3-måneders periode høsten 2007 og som omhandlet operasjonspreparater med colorectal cancer, ble vurdert mhp type rapportering og rapportering av 11 nøkkelvariabler. Av de 20 laboratoriene som besvarte operasjonspreparater med colorectal cancer, hadde 16 skrevne retningslinjer for rapportering. Av disse brukte 4 den nasjonale elektroniske mal, 5 brukte sjekkliste, 3 brukte lokalt utviklet elektronisk templat, mens 4 verken brukte mal eller sjekkliste. Av de 650 rapportene, som var sendt Kreftregisteret i den aktuelle 3 måneders perioden, var den nasjonale malen blitt brukt i 170 rapporter (26%), sjekkliste/lokal elektronisk mal i 112 (17%) og fritekst i 368 (57%) rapporter. Bruk av nasjonal elektronisk mal forbedret signifikant (p<0,05) rapporteringen av 11 nøkkelvariabler sammenlignet med sjekklister, lokalt utviklet elektronisk mal og fritekst. Rapporten viser at en standardisert patologirapport sikrer en fullstendig besvarelse. Ulike årsaker for å forklare hvorfor bruk av en slik rapporteringsform ikke nyttes i større utstrekning ved norske patologilaboratorier, blir diskutert

Teinefiske etter dypvannsreke (Pandalus borealis) i Norge - Kommersielle landinger og sammenligning av teinefiske i tre områder langs kysten

Dypvannsreken (Pandalus borealis) er en av de viktigste kommersielle krepsdyrartene i Norge. Reker fiskes primært med bunntrål. I Nord-Atlanteren landes det 250 000–400 000 tonn årlig, mens det kystnært i Norge i 2021 ble trålt omtrent 3000 tonn. De norske kystnære trålfangstene har vist en negativ utvikling de senere årene. Kystnært fiske etter dypvannsreker ved hjelp av teiner startet i det nordøstlige USA i 1971, og fangstratene ble regnet som gode. Forsøk med teinefiske etter reker i Norge startet på slutten av 1970-tallet, men frem til nylig har ikke disse forsøkene vært vellykkede. I denne rapporten beskrives fremveksten av det kommersielle teinefisket i Norge, både fordelingen langs kysten og i kvanta. Basert på resultater fra reketeinefiske i tre forskjellige områder, og ved å sammenligne disse resultatene med resultater fra et prøvefiske i Finnmark i 2015–2017 og et reketeinefiske i Nova Scotia, diskuteres muligheter og begrensninger for utvikling av et lønnsomt reketeinefiske i Norge. Teinefangstene er fortsatt ubetydelige sammenlignet med trålfangster. Det ble observert en signifikant redskapseffekt i de tre undersøkte områdene, der det med trål gjennomgående ble fanget en større andel småreker enn med teiner. Reketeinefiske er fortsatt på eksperimentstadiet i Norge, og det finnes fremdeles mange områder hvor reketeinefiske ikke er testet ut.Teinefiske etter dypvannsreke (Pandalus borealis) i Norge - Kommersielle landinger og sammenligning av teinefiske i tre områder langs kystenpublishedVersio

Wear particles and ions from cemented and uncemented titanium-based hip prostheses-A histological and chemical analysis of retrieval material

Wear debris-induced inflammation is considered to be the main cause for periprosthetic osteolysis in total hip replacements (THR). The objective of this retrieval study was to examine the tissue reactions and exposure to metal ions and wear particles in periprosthetic tissues and blood samples from patients with titanium (Ti)-based hip prostheses that were revised due to wear, osteolysis, and/or aseptic loosening. Semiquantitative, histological tissue evaluations in 30 THR-patients revealed numerous wear debris-loaded macrophages, inflammatory cells, and necrosis in both groups. Particle load was highest in tissues adjacent to loosened cemented Ti stems that contained mainly submicron zirconium (Zr) dioxide particles. Particles containing pure Ti and Ti alloy elements were most abundant in tissues near retrieved uncemented cups. Polyethylene particles were also detected, but accounted only for a small portion of the total particle number. The blood concentrations of Ti and Zr were highly elevated in cases with high abrasive wear and osteolysis. Our findings indicate that wear particles of different chemical composition induced similar inflammatory responses, which suggests that particle size and load might be more important than the wear particle composition in periprosthetic inflammation and osteolysis

HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL. A population-based follow-up study from Western Norway

In Norway, Pap smears with atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are triaged after 6 months. The aim of the study was to evaluate effects of implementing human papillomavirus (HPV) test (2005) in delayed triage of ASCUS and LSIL in a cohort of women from Western Norway. After a survey of 119,469 cervical Pap smears during 2005–2007, a total of 1055 women with an index ASCUS or LSIL were included in the study and followed up for 3–6 years with respect to progression into cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Overall sensitivity for detection of CIN2+ with HPV testing and cytology was 96% and 72%, respectively. The sensitivity for detection of CIN2+ was not affected by age, but the specificity of the HPV test increased with age. Thus, for the age groups 50 years, the specificity of a positive HPV test to detect CIN2+ was 47%, 71%, and 82%, respectively. Positive predictive values for CIN2+ in women with positive cytology, positive HPV test, negative cytology, negative HPV test, or negative HPV and cytology tests were 52%, 41%, 8%, 1.5%, and 0.4%, respectively. HPV testing resulted in a net 22% increased detection of CIN2+. Fifty-six percent of CIN2+ was detected at an earlier time point with HPV testing in triage. Implementation of HPV testing in delayed triage of ASCUS and LSIL improved the stratification of CIN2+ risk and increased CIN2+ detection and at an earlier time point than with triage by cytology alon