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Stian Knappskogs bilde

Stian Knappskog

Professor
  • E-postStian.Knappskog@uib.no
  • Telefon+47 55 97 64 47+47 970 46 719
  • Besøksadresse
    Haukeland universitetssykehus, Laboratoriebygget
  • Postadresse
    Postboks 7804
    5020 Bergen

Genetiske mekanismar som gir resistens mot behandling hos kreftpasientar

Nokon kreftpasientar opplever dårlig effekt av behandlinga. Vår forsking fokuserer på genetiske og molekylære mekanismar som gjer at enkelt-svulstar ikkje responderer på ulike kreft-medikament. Målet med er å identifisere genetiske mekanismar som kan nyttast som såkalla prediktive biomarkørar, dvs markørar som kan indikere kva for type cellegift som vil være mest nyttig for kvar enkelt pasient.

 

Nøkkel-publikasjonar:

Eikesdal et al. Annals of Oncology, 2021

Knappskog et al. Molecular Oncology, 2015

Knappskog et al. Breast Cancer Research, 2012

 

 

Medfødte variantar som påvirkar kreftrisiko

I tillegg til genvariantar som endrar aminosyrerekkjefølgja i protein, kan kreftrisiko vere påvirka av variantar som ligg i ikkje-proteinkodande delar av DNA eller i mekanismar som styrer korleis eit gen vert uttrykt. Vi jobbar med variantar som ligg i promoterområdene til gen som er involvert i kreftutvikling. Vi jobbar særskilt med variantar i promoteren til MDM2-genet, der vi m.a. har identifisert ein variant (SNP285) som gir 37% redusert risiko for brystkreft og 39% redusert risiko for eggstokkreft i nokre grupper av europeiske kvinner. I tillegg jobbar vi med regulering av BRCA1 genet, der vi har funne at medfødt feil-regulering gir 2-3 gonger auka risiko for eggstokkreft.

 

Nøkkel-publikasjonar:

Lønning et al. Annals of Internal Medicine, 2018

Knappskog et al. European Journal of Cancer 2012

Knappskog et al. Cancer Cell, 2011

 

 

Kreftheterogenitet og evolusjon

Mange kreftsvulstar er heterogene, og er bygd opp av subklonar som er genetisk ulike. Vår forsking fokuserer på korleis ulike subklonar vekst og ter seg gjennom sjukdomsforløpet. Dette inkluderer kva som skjer når sjukdommen spreier seg i kroppen, og kva som skjer når pasienten får behandling med ulike typar medikament.

 

Nøkkel-publikasjonar:

Yates et al. Cancer Cell, 2017

Yates et al. Nature Medicine, 2015

Løes et al. International Journal of Cancer, 2016

Innslag i Dagsrevyen om funn i PETREMAC-studien (2021.04.15)

Åse vart kreftfri etter «umogeleg» behandling – NRK Vestland

 

Avisreportasje om nytt sekvenseringsinstrument (2019.10.02)

https://www.bt.no/nyheter/lokalt/i/6jeX98/kreftforskerne-vet-ikke-hvorfor-noen-svulster-ikke-reagerer-paa-behandl

 

Avisreportasjer om forskingsfunn og publikasjon  (2018.01.16)

https://www.vg.no/forbruker/helse/i/G1QO46/norske-forskere-med-internasjonalt-gjennombrudd-kan-pavise-kreftrisiko-i-ufodte-barn

https://www.bt.no/nyheter/innenriks/i/oR617R/Norske-forskere-kan-pavise-kreftrisiko-hos-ufodte-barn

 

Avisreportasjer om forskingsfunn og publikasjon  (2017.08.14)

http://www.vg.no/nyheter/innenriks/helse-og-medisin/norske-forskere-med-nytt-gjennombrudd-kan-gi-bedre-behandling-av-brystkreft/a/24115097/

https://www.ba.no/helse/haukeland-universitetssykehus/nyheter/bergensforskere-med-kreftgjennombrudd/s/5-8-631593

 

Avisreportasje om Ung Forsker-pris ved Onkologisk Forum (2016.11.18)

https://www.dagensmedisin.no/artikler/2016/11/18/stian-knappskog-far-ung-forsker-prisen-2016/?acceptCookies=true

 

TV-innslag om ny klinisk studie - PETREMAC (2016.07.03)

http://www.tv2.no/a/8421737/

 

TV-innslag om ny klinisk studie - PETREMAC (2016.07.05)

http://www.tv2.no/a/8428791/

 

Avisreportasje om forsking finansiert av Rosa sløyfe-aksjonen (2015.10.29)

http://www.ba.no/nyheter/helsevesen/medisin-og-helse/her-gar-midlene-fra-rosa-sloyfe/s/5-8-183805

 

TV intervju om donasjon frå Mohn (2014.12.23)

https://tv.nrk.no/sok?q=Stian%20Knappskog&filter=rettigheter

 

Film for Kreftforeningen angåande Rosa sløyfe-aksjonen (2013.09.20)

https://www.youtube.com/watch?v=Sr4qk4RKz3I

 

Avisreportasje om oppdaging av genvariant som reduserer kreftrisiko (2011.02.15)

http://www.vg.no/nyheter/innenriks/helse-og-medisin/fant-supergen-som-beskytter-mot-kreft/a/10038307/

http://www.forskningsradet.no/prognett-kreftsatsing/Nyheter/Genvariant_reduserer_kreftrisiko/1253964771715&lang=no

 

 

Publikasjonar lista i PubMed:

https://www.ncbi.nlm.nih.gov/pubmed/?term=knappskog+s

 

Publikasjonar lista i Cristin:

  • Vis forfatter(e) 2020. The novel microRNAs hsa-miR-nov7 and hsamiR- nov3 are over-expressed in locally advanced breast cancer. PLOS ONE. 1-23.
  • Vis forfatter(e) 2020. Sex differences in oncogenic mutational processes. Nature Communications. 1-24.
  • Vis forfatter(e) 2020. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples. Nature Communications. 1-27.
  • Vis forfatter(e) 2020. Pan-cancer analysis of whole genomes. Nature. 82-93.
  • Vis forfatter(e) 2020. Olaparib monotherapy as primary treatment in unselected triple negative breast cancer. Annals of Oncology. 1-10.
  • Vis forfatter(e) 2020. Golgi-Localized PAQR4 Mediates Antiapoptotic Ceramidase Activity in Breast Cancer. Cancer Research. 2163-2174.
  • Vis forfatter(e) 2020. Assessment of tumor suppressor promoter methylation in healthy individuals. Clinical Epigenetics. 1-15.
  • Vis forfatter(e) 2019. ctDNA detected by ddPCR reveals changes in tumour load in metastatic malignant melanoma treated with bevacizumab. Scientific Reports. 1-15.
  • Vis forfatter(e) 2019. The circular RNome of primary breast cancer. Genome Research. 356-366.
  • Vis forfatter(e) 2019. Rethinking Gynecological High- Grade Serous Carcinoma. Portraying the p53 isoform landscape and development of a new preclinical for optical imaging in xenograft models.
  • Vis forfatter(e) 2019. Neoadjuvant olaparib monotherapy in primary triple negative breast cancer.
  • Vis forfatter(e) 2019. Neoadjuvant endocrine therapy with palbociclib in patients with high-risk breast cancer.
  • Vis forfatter(e) 2019. Mutation analysis by deep sequencing of pancreatic juice from patients with pancreatic ductal adenocarcinoma. BMC Cancer. 1-12.
  • Vis forfatter(e) 2019. Influence of p53 isoform expression on survival in high-grade serous ovarian cancers. Scientific Reports. 1-11.
  • Vis forfatter(e) 2019. Epithelial to mesenchymal transition (EMT) is associated with attenuation of succinate dehydrogenase (SDH) in breast cancer through reduced expression of SDHC. Cancer & Metabolism.
  • Vis forfatter(e) 2019. Effective treatment of metastatic melanoma by combining mapk and pi3k signaling pathway inhibitors. International Journal of Molecular Sciences. 1-19.
  • Vis forfatter(e) 2019. Constitutional mosaic epimutations - A hidden cause of cancer? Cell stress. 118-135.
  • Vis forfatter(e) 2018. White blood cell BRCA1 promoter methylation status and ovarian cancer risk. Annals of Internal Medicine. 326-334.
  • Vis forfatter(e) 2018. Patterns of genomic evolution in advanced melanoma. Nature Communications. 1-12.
  • Vis forfatter(e) 2018. Introducing nano-scale quantitative polymerase chain reaction. Biochemical and Biophysical Research Communications - BBRC. 923-926.
  • Vis forfatter(e) 2018. High expression of the p53 isoform ? is associated with reduced progression-free survival in uterine serous carcinoma. BMC Cancer. 1-10.
  • Vis forfatter(e) 2018. Genomic evolution and therapy resistance in melanoma and breast cancer.
  • Vis forfatter(e) 2018. BRCA1 methylation in newborns: Genetic disposition, maternal transfer, environmental influence, or by chance only? Clinical Epigenetics.
  • Vis forfatter(e) 2018. Association of rs2279744 and rs117039649 promoter polymorphism with the risk of gynaecological cancer: A meta-analysis of case-control studies . Medicine.
  • Vis forfatter(e) 2017. Tumor cells interact with red blood cells via galectin-4 - a short report. Cellular Oncology. 1-9.
  • Vis forfatter(e) 2017. The Functional roles of the MDM2 splice variants P2-MDM2-10 and MDM2-∆5 in breast cancer cells. Translational Oncology. 806-817.
  • Vis forfatter(e) 2017. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo. Nature. 714-718.
  • Vis forfatter(e) 2017. MDM2 promoter polymorphism del1518 (rs3730485) and its impact on endometrial and ovarian cancer risk. BMC Cancer. 1-6.
  • Vis forfatter(e) 2017. Impact of the MDM2 splice-variants MDM2-A, MDM2-B and MDM2-C on cytotoxic stress response in breast cancer cells. BMC Cell Biology. 1-9.
  • Vis forfatter(e) 2017. High PTEN gene expression is a negative prognostic marker in human primary breast cancers with preserved p53 function. Breast Cancer Research and Treatment. 177-190.
  • Vis forfatter(e) 2017. Genomic evolution of breast cancer metastasis and relapse. Cancer Cell. 169-184.e7.
  • Vis forfatter(e) 2017. Effects of concomitant inactivation of p53 and pRb on response to doxorubicin treatment in breast cancer cell lines. Cell death discovery.
  • Vis forfatter(e) 2017. Activation of Akt characterizes estrogen receptor positive human breast cancers which respond to anthracyclines. OncoTarget. 41227-41241.
  • Vis forfatter(e) 2017. APOBEC3A/B deletion polymorphism and cancer risk. Carcinogenesis. 118-124.
  • Vis forfatter(e) 2016. Treatment with aromatase inhibitors stimulates the expression of epidermal growth factor receptor-1 and neuregulin 1 in ER positive/HER-2/neu non-amplified primary breast cancers. Journal of Steroid Biochemistry and Molecular Biology. 228-235.
  • Vis forfatter(e) 2016. The MDM4 SNP34091 (rs4245739) C-allele is associated with increased risk of ovarian—but not endometrial cancer. Tumour Biology. 10697-10702.
  • Vis forfatter(e) 2016. Promoter SNPs rs116896264 and rs73933062 form a distinct haplotype and are associated with galectin-4 overexpression in colorectal cancer. Mutagenesis. 401-408.
  • Vis forfatter(e) 2016. Prevalence of the CHEK2 R95* germline mutation. Hereditary Cancer in Clinical Practice. 4 sider.
  • Vis forfatter(e) 2016. MDM2 promoter SNP55 (rs2870820) affects risk of colon cancer but not breast-, lung-, or prostate cancer. Scientific Reports. 8 sider.
  • Vis forfatter(e) 2016. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature. 47-54.
  • Vis forfatter(e) 2016. Intra-patient inter-metastatic genetic heterogeneity in colorectal cancer as a key determinant of survival after curative liver resection. PLoS Genetics. 22 sider.
  • Vis forfatter(e) 2016. Impact of KRAS, BRAF, PIK3CA, TP53 status and intraindividual mutation heterogeneity on outcome after liver resection for colorectal cancer metastases. International Journal of Cancer. 647-656.
  • Vis forfatter(e) 2016. EGFRvIII mutations can emerge as late and heterogenous events in glioblastoma development and promote angiogenesis through Src activation. Neuro-Oncology. 1644-1655.
  • Vis forfatter(e) 2016. Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration. Nature Communications.
  • Vis forfatter(e) 2016. Associations between the MDM2 promoter P1 polymorphism del1518 (rs3730485) and incidence of cancer of the breast, lung, colon and prostate. OncoTarget. 28637-28646.
  • Vis forfatter(e) 2015. Subclonal diversification of primary breast cancer revealed by multiregion sequencing. Nature Medicine. 751-759.
  • Vis forfatter(e) 2015. Performance comparison of three BRAF V600E detection methods in malignant melanoma and colorectal cancer specimen. Tumour Biology. 1003-1013.
  • Vis forfatter(e) 2015. MDM4 SNP34091 (rs4245739) and its effect on breast-, colon-, lung-, and prostate cancer risk. Cancer Medicine. 1901-1907.
  • Vis forfatter(e) 2015. Influence of MDM2 SNP309 and SNP285 status on the risk of cancer in the breast, prostate, lung and colon. International Journal of Cancer. 96-103.
  • Vis forfatter(e) 2015. Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells. Genome Research. 814-824.
  • Vis forfatter(e) 2015. Estrogens correlate with PELP1 expression in ER positive breast cancer. PLOS ONE. 12 sider.
  • Vis forfatter(e) 2015. Concomitant inactivation of the p53- and pRB- functional pathways predicts resistance to DNA damaging drugs in breast cancer in vivo. Molecular Oncology. 1553-1564.
  • Vis forfatter(e) 2014. TP53 status predicts long-term survival in locally advanced breast cancer after primary chemotherapy. Acta Oncologica. 1347-1355.
  • Vis forfatter(e) 2014. Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649). OncoTarget. 8223-8234.
  • Vis forfatter(e) 2014. MDM2 SNP309 and risk of endometrial cancer. Tumour Biology.
  • Vis forfatter(e) 2014. MDM2 SNP309 and risk of cervical cancer. Tumour Biology. 6185-6186.
  • Vis forfatter(e) 2014. MDM2 SNP309 and risk of cervical cancer. Tumour Biology.
  • Vis forfatter(e) 2014. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes. Science.
  • Vis forfatter(e) 2014. Effects of SNP variants in the 17β-HSD2 and 17β-HSD7 genes and 17β-HSD7 copy number on gene transcript and estradiol levels in breast cancer tissue. Journal of Steroid Biochemistry and Molecular Biology. 192-198.
  • Vis forfatter(e) 2014. Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer. Nature Genetics. 487-491.
  • Vis forfatter(e) 2013. Signatures of mutational processes in human cancer. Nature. 415-421.
  • Vis forfatter(e) 2013. Outcome after surgery for primary hyperaldosteronism may depend on KCNJ5 tumor mutation status: a population-based study from Western Norway. Langenbeck's archives of surgery (Print). 869-874.
  • Vis forfatter(e) 2013. Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers. Oncogene. 5315-5330.
  • Vis forfatter(e) 2013. MDM2 SNP309 and risk of endometrial cancer. Polish Journal of Pathology. 69-70.
  • Vis forfatter(e) 2013. Low BRAF and NRAS expression levels are associated with clinical benefit from DTIC therapy and prognosis in metastatic melanoma. Clinical and Experimental Metastasis. 867-876.
  • Vis forfatter(e) 2013. Inverse regulation of EGFR/HER1 and HER2-4 in normal and malignant human breast tissue. PLOS ONE. 12 sider.
  • Vis forfatter(e) 2013. Functional characterisation of p53 mutants identified in breast cancers with suboptimal responses to anthracyclines or mitomycin. Biochimica et Biophysica Acta - General Subjects. 2790-2797.
  • Vis forfatter(e) 2013. CXXC5 (retinoid-inducible nuclear factor, RINF) is a potential therapeutic target in high-risk human acute myeloid leukemia. OncoTarget. 1438-1448.
  • Vis forfatter(e) 2012. Synergistic induction of p53 mediated apoptosis by valproic acid and nutlin-3 in acute myeloid leukemia. Leukemia. 910-917.
  • Vis forfatter(e) 2012. SNP285C modulates oestrogen receptor/Sp1 binding to the MDM2 promoter and reduces the risk of endometrial but not prostatic cancer. European Journal of Cancer. 1988-1996.
  • Vis forfatter(e) 2012. Re: Murine double minute 2 promoter SNP309 polymorphism and prostate cancer risk: a meta-analysis. International journal of urology. 966-966.
  • Vis forfatter(e) 2012. P53 and its molecular basis to chemoresistance in breast cancer. Expert opinion on therapeutic targets. S23-S30.
  • Vis forfatter(e) 2012. MDM2 Promoter SNP344T>A (rs1196333) Status Does Not Affect Cancer Risk. PLOS ONE. 6 sider.
  • Vis forfatter(e) 2012. Low expression levels of ATM may substitute for CHEK2/TP53 mutations predicting resistance towards anthracycline and mitomycin chemotherapy in breast cancer. Breast Cancer Research. 12 sider.
  • Vis forfatter(e) 2012. Elevated levels of the steroidogenic factor 1 are associated with over-expression of CYP19 in an oestrogen-producing testicular Leydig cell tumour. European Journal of Endocrinology. 941-949.
  • Vis forfatter(e) 2012. Effect of the MDM2 promoter polymorphisms SNP309T>G and SNP285G>C on the risk of ovarian cancer in BRCA1 mutation carriers. BMC Cancer. 6 sider.
  • Vis forfatter(e) 2012. Effect of CYP19 rs6493497 and rs7176005 haplotype status on in vivo aromatase transcription, plasma and tissue estrogen levels in postmenopausal women. Journal of Steroid Biochemistry and Molecular Biology. 69-75.
  • Vis forfatter(e) 2012. Correlation analysis of p53 protein isoforms with NPM1/FLT3 mutations and therapy response in acute myeloid leukemia. Oncogene. 1533-1545.
  • Vis forfatter(e) 2012. Chemosensitivity and p53; new tricks by an old dog. Breast Cancer Research. 325.
  • Vis forfatter(e) 2011. The nuclear receptor coactivator PELP1/MNAR is positively correlated with estrogen levels in breast cancer patients.
  • Vis forfatter(e) 2011. The MDM2 Promoter SNP285C/309G Haplotype Diminishes Sp1 Transcription Factor Binding and Reduces Risk for Breast and Ovarian Cancer in Caucasians. Cancer Cell. 273-282.
  • Vis forfatter(e) 2011. Recent data on intratumor estrogens in breast cancer. Steroids. 786-791.
  • Vis forfatter(e) 2011. RINF (CXXC5) is overexpressed in solid tumors and is an unfavorable prognostic factor in breast cancer(dagger). Annals of Oncology. 2208-2215.
  • Vis forfatter(e) 2011. Predictive and Prognostic Impact of TP53 Mutations and MDM2 Promoter Genotype in Primary Breast Cancer Patients Treated with Epirubicin or Paclitaxel. PLOS ONE. 10 sider.
  • Vis forfatter(e) 2011. MDM2 promoter SNP285 and SNP309; phylogeny and impact on cancer risk. OncoTarget. 251-258.
  • Vis forfatter(e) 2011. Exploring breast cancer estrogen disposition: The basis for endocrine manipulation. Clinical Cancer Research. 4948-4958.
  • Vis forfatter(e) 2011. Effects of the MDM2 promoter SNP285 and SNP309 on Sp1 transcription factor binding and cancer risk. Transcription.
  • Vis forfatter(e) 2011. Clinical effect of Temozolomide-based chemotherapy in poorly differentiated endocrine carcinoma after progression on first-line chemotherapy. Cancer. 4617-4622.
  • Vis forfatter(e) 2011. Alterations of the retinoblastoma gene in metastatic breast cancer. Clinical and Experimental Metastasis. 319-326.
  • Vis forfatter(e) 2010. Spontaneous Malignant Transformation of Human Mesenchymal Stem Cells Reflects Cross-Contamination: Putting the Research Field on Track - Letter. Cancer Research. 6393-6396.
  • Vis forfatter(e) 2010. Identification and characterization of retinoblastoma gene mutations disturbing apoptosis in human breast cancers. Molecular Cancer. 13 sider.
  • Vis forfatter(e) 2010. Gene Expression Profiling-Based Identification of Molecular Subtypes in Stage IV Melanomas with Different Clinical Outcome. Clinical Cancer Research. 3356-3367.
  • Vis forfatter(e) 2010. Epidermal growth factor receptors (ErbB/HER) and the ligand Neuregulin 1 (NRG1) increase in breast tumors during short time treatment with aromatase inhibitors.
  • Vis forfatter(e) 2010. Alterations in the p53 Pathway and p16INK4a Expression Predict Overall Survival in Metastatic Melanoma Patients Treated with Dacarbazine. Journal of Investigative Dermatology. 2514-2516.
  • Vis forfatter(e) 2008. CHEK2 mutations affecting kinase activity together with mutations in TP53 indicate a functional pathway associated with resistance to epirubicin in primary breast cancer. PLOS ONE. 15 sider.
  • Vis forfatter(e) 2007. UTRech tm: Exploiting mRNA Targeting To Increase Protein Secetion From Mammalian Cells. 8 sider.
  • Vis forfatter(e) 2007. The level of synthesis and secretion of Gaussia princeps luciferase in transfected CHO cells is heavily dependent on the choice of signal peptide. Journal of Biotechnology. 705-715.
  • Vis forfatter(e) 2007. The MDM2 SNP309 G/T promoter polymorphism is associated with chemoresistance in primary breast cancers harbouring mutations in the TP53 gene.
  • Vis forfatter(e) 2007. P21/waf1 mutation and drug resistance to paclitaxel in locally advanced breast cancer. International Journal of Cancer. 2749-2749.
  • Vis forfatter(e) 2007. Mutations and polymorphisms of the p21B transcript in breast cancer. International Journal of Cancer. 908-910.
  • Vis forfatter(e) 2007. Germline Genetic Alterations Affecting CDKN2A, MDM2 and CDKN1A in Melanoma and Breast Cancer Patients.
  • Vis forfatter(e) 2007. Breast cancer prognostication and prediction in the postgenomic era. Annals of Oncology. 1293-1306.
  • Vis forfatter(e) 2007. Adjuvant treatment: the contribution of expression microarrays. Breast Cancer Research.
  • Vis forfatter(e) 2006. The novel p21 polymorphism p21(G251A) is associated with locally advanced breast cancer. Clinical Cancer Research. 6000-6004.
  • Vis forfatter(e) 2006. Functional characterisation of novel p53 mutants.
  • Vis forfatter(e) 2006. A novel type of deletion in the CDKN2A gene identified in a melanoma-prone family. Genes, Chromosomes and Cancer. 1155-1163.
  • Vis forfatter(e) 2005. The SNP309HDM2 polymorphism is associated with chemoresistance and poor survival in breast cancers harboring mutations in the TP53 gene. Breast Cancer Research and Treatment. S160-S160.

Se fullstendig oversikt over publikasjoner i CRIStin.

Cancer Genome Project, Wellcome Trust Sanger Institute, Cambridge, UK

http://www.sanger.ac.uk/

 

Norsk Kreftgenomikk Konsortium(NCGC)

http://kreftgenomikk.no/en/