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Stian Knappskog's picture

Stian Knappskog

Professor
  • E-mailStian.Knappskog@uib.no
  • Phone+47 55 97 64 47+47 970 46 719
  • Visitor Address
    Haukeland universitetssykehus, Laboratoriebygget
  • Postal Address
    Postboks 7804
    5020 Bergen

Genetic mechanisms causing resistance to therapy among cancer patients.

Some cancer patients experience poor effects of therapy. Our research focuses on the genetic and molecular mechanisms causing some tumours not to respond to therapy. The aim is to identify genetic alterations that can be used as predictive biomarkers, i.e. markers that can predict what kind of therapy would be most beneficial for each individual patient.

 

Key publications:

Eikesdal et al. Annals of Oncology, 2021

Knappskog et al. Molecular Oncology, 2015

Knappskog et al. Breast Cancer Research, 2012

 

 

Genetic variants modulating cancer risk

In addition to variants changing the genetic code within a protein coding region of DNA, cancer risk may be influenced by variations in the non-coding regions of DNA and in regulatory mechanism for gene expression. We are assessing common polymorphisms in promoter regions of genes involved in cancer. We are currently focusing on polymorphisms in the promoter of the MDM2 gene, where we have found one particular variant (SNP285) to reduce the risk of breast cancer with 37% and the risk of ovarian cancer with 39% in some subgroups of Caucasian women. Also, we are focusing on the regulation of the BRCA1 gene, where we have found de-regulation to cause a 2-3 fold increased risk of ovarian cancer.

 

Key publications:

Lønning et al. Annals of Internal Medicine, 2018

Knappskog et al. European Journal of Cancer 2012

Knappskog et al. Cancer Cell, 2011

 

 

Intratumor heterogeneity

Many tumours have proven to be heterogenous and consist of genetically different subclones. Our research assesses the interplay of different sublcones with respect to tumour progression and metastasis as well as response to treatment.

 

Key publications:

Yates et al. Cancer Cell, 2017

Yates et al. Nature Medicine, 2015

Løes et al. International Journal of Cancer, 2016

Newspaper report about new Sequencer (2019.10.02)

 

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

 

 

Newspaper stories about major publication (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

 

 

Newspaper stories about major publication (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

 

 

 

Newspaper story about National Young Scientist award (2016.11.18)

 

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

 

 

TV case about the novel clinical trial PETREMAC (2016.07.03)

 

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

 

 

TV case about the novel clinical trial PETREMAC (2016.07.05)

 

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

 

 

Newspaper story about research funded by the Pink ribbon campaign (2015.10.29)

 

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

 

 

TV interview about Mohn donation to research (2014.12.23)

 

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

 

 

Film for the Norwegian Cancer Society’s Pink Ribbon Campaign (2013.09.20)

 

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

 

 

 

Newspaper story about the discovery of cancer risk reducing polymorphism (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

 

 

Publications registered in PubMed:

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

 

Publications registered in CRIStin:

 

  • Show author(s) 2020. The novel microRNAs hsa-miR-nov7 and hsamiR- nov3 are over-expressed in locally advanced breast cancer. PLOS ONE. 1-23.
  • Show author(s) 2020. Sex differences in oncogenic mutational processes. Nature Communications. 1-24.
  • Show author(s) 2020. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples. Nature Communications. 1-27.
  • Show author(s) 2020. Pan-cancer analysis of whole genomes. Nature. 82-93.
  • Show author(s) 2020. Olaparib monotherapy as primary treatment in unselected triple negative breast cancer. Annals of Oncology. 1-10.
  • Show author(s) 2020. Golgi-Localized PAQR4 Mediates Antiapoptotic Ceramidase Activity in Breast Cancer. Cancer Research. 2163-2174.
  • Show author(s) 2020. Assessment of tumor suppressor promoter methylation in healthy individuals. Clinical Epigenetics. 1-15.
  • Show author(s) 2019. ctDNA detected by ddPCR reveals changes in tumour load in metastatic malignant melanoma treated with bevacizumab. Scientific Reports. 1-15.
  • Show author(s) 2019. The circular RNome of primary breast cancer. Genome Research. 356-366.
  • Show author(s) 2019. Rethinking Gynecological High- Grade Serous Carcinoma. Portraying the p53 isoform landscape and development of a new preclinical for optical imaging in xenograft models.
  • Show author(s) 2019. Neoadjuvant olaparib monotherapy in primary triple negative breast cancer.
  • Show author(s) 2019. Neoadjuvant endocrine therapy with palbociclib in patients with high-risk breast cancer.
  • Show author(s) 2019. Mutation analysis by deep sequencing of pancreatic juice from patients with pancreatic ductal adenocarcinoma. BMC Cancer. 1-12.
  • Show author(s) 2019. Influence of p53 isoform expression on survival in high-grade serous ovarian cancers. Scientific Reports. 1-11.
  • Show author(s) 2019. Epithelial to mesenchymal transition (EMT) is associated with attenuation of succinate dehydrogenase (SDH) in breast cancer through reduced expression of SDHC. Cancer & Metabolism.
  • Show author(s) 2019. Effective treatment of metastatic melanoma by combining mapk and pi3k signaling pathway inhibitors. International Journal of Molecular Sciences. 1-19.
  • Show author(s) 2019. Constitutional mosaic epimutations - A hidden cause of cancer? Cell stress. 118-135.
  • Show author(s) 2018. White blood cell BRCA1 promoter methylation status and ovarian cancer risk. Annals of Internal Medicine. 326-334.
  • Show author(s) 2018. Patterns of genomic evolution in advanced melanoma. Nature Communications. 1-12.
  • Show author(s) 2018. Introducing nano-scale quantitative polymerase chain reaction. Biochemical and Biophysical Research Communications - BBRC. 923-926.
  • Show author(s) 2018. High expression of the p53 isoform ? is associated with reduced progression-free survival in uterine serous carcinoma. BMC Cancer. 1-10.
  • Show author(s) 2018. Genomic evolution and therapy resistance in melanoma and breast cancer.
  • Show author(s) 2018. BRCA1 methylation in newborns: Genetic disposition, maternal transfer, environmental influence, or by chance only? Clinical Epigenetics.
  • Show author(s) 2018. Association of rs2279744 and rs117039649 promoter polymorphism with the risk of gynaecological cancer: A meta-analysis of case-control studies . Medicine.
  • Show author(s) 2017. Tumor cells interact with red blood cells via galectin-4 - a short report. Cellular Oncology. 1-9.
  • Show author(s) 2017. The Functional roles of the MDM2 splice variants P2-MDM2-10 and MDM2-∆5 in breast cancer cells. Translational Oncology. 806-817.
  • Show author(s) 2017. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo. Nature. 714-718.
  • Show author(s) 2017. MDM2 promoter polymorphism del1518 (rs3730485) and its impact on endometrial and ovarian cancer risk. BMC Cancer. 1-6.
  • Show author(s) 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.
  • Show author(s) 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.
  • Show author(s) 2017. Genomic evolution of breast cancer metastasis and relapse. Cancer Cell. 169-184.e7.
  • Show author(s) 2017. Effects of concomitant inactivation of p53 and pRb on response to doxorubicin treatment in breast cancer cell lines. Cell death discovery.
  • Show author(s) 2017. Activation of Akt characterizes estrogen receptor positive human breast cancers which respond to anthracyclines. OncoTarget. 41227-41241.
  • Show author(s) 2017. APOBEC3A/B deletion polymorphism and cancer risk. Carcinogenesis. 118-124.
  • Show author(s) 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.
  • Show author(s) 2016. The MDM4 SNP34091 (rs4245739) C-allele is associated with increased risk of ovarian—but not endometrial cancer. Tumour Biology. 10697-10702.
  • Show author(s) 2016. Promoter SNPs rs116896264 and rs73933062 form a distinct haplotype and are associated with galectin-4 overexpression in colorectal cancer. Mutagenesis. 401-408.
  • Show author(s) 2016. Prevalence of the CHEK2 R95* germline mutation. Hereditary Cancer in Clinical Practice. 4 pages.
  • Show author(s) 2016. MDM2 promoter SNP55 (rs2870820) affects risk of colon cancer but not breast-, lung-, or prostate cancer. Scientific Reports. 8 pages.
  • Show author(s) 2016. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature. 47-54.
  • Show author(s) 2016. Intra-patient inter-metastatic genetic heterogeneity in colorectal cancer as a key determinant of survival after curative liver resection. PLoS Genetics. 22 pages.
  • Show author(s) 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.
  • Show author(s) 2016. EGFRvIII mutations can emerge as late and heterogenous events in glioblastoma development and promote angiogenesis through Src activation. Neuro-Oncology. 1644-1655.
  • Show author(s) 2016. Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration. Nature Communications.
  • Show author(s) 2016. Associations between the MDM2 promoter P1 polymorphism del1518 (rs3730485) and incidence of cancer of the breast, lung, colon and prostate. OncoTarget. 28637-28646.
  • Show author(s) 2015. Subclonal diversification of primary breast cancer revealed by multiregion sequencing. Nature Medicine. 751-759.
  • Show author(s) 2015. Performance comparison of three BRAF V600E detection methods in malignant melanoma and colorectal cancer specimen. Tumour Biology. 1003-1013.
  • Show author(s) 2015. MDM4 SNP34091 (rs4245739) and its effect on breast-, colon-, lung-, and prostate cancer risk. Cancer Medicine. 1901-1907.
  • Show author(s) 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.
  • Show author(s) 2015. Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells. Genome Research. 814-824.
  • Show author(s) 2015. Estrogens correlate with PELP1 expression in ER positive breast cancer. PLOS ONE. 12 pages.
  • Show author(s) 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.
  • Show author(s) 2014. TP53 status predicts long-term survival in locally advanced breast cancer after primary chemotherapy. Acta Oncologica. 1347-1355.
  • Show author(s) 2014. Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649). OncoTarget. 8223-8234.
  • Show author(s) 2014. MDM2 SNP309 and risk of endometrial cancer. Tumour Biology.
  • Show author(s) 2014. MDM2 SNP309 and risk of cervical cancer. Tumour Biology. 6185-6186.
  • Show author(s) 2014. MDM2 SNP309 and risk of cervical cancer. Tumour Biology.
  • Show author(s) 2014. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes. Science.
  • Show author(s) 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.
  • Show author(s) 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.
  • Show author(s) 2013. Signatures of mutational processes in human cancer. Nature. 415-421.
  • Show author(s) 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.
  • Show author(s) 2013. Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers. Oncogene. 5315-5330.
  • Show author(s) 2013. MDM2 SNP309 and risk of endometrial cancer. Polish Journal of Pathology. 69-70.
  • Show author(s) 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.
  • Show author(s) 2013. Inverse regulation of EGFR/HER1 and HER2-4 in normal and malignant human breast tissue. PLOS ONE. 12 pages.
  • Show author(s) 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.
  • Show author(s) 2013. CXXC5 (retinoid-inducible nuclear factor, RINF) is a potential therapeutic target in high-risk human acute myeloid leukemia. OncoTarget. 1438-1448.
  • Show author(s) 2012. Synergistic induction of p53 mediated apoptosis by valproic acid and nutlin-3 in acute myeloid leukemia. Leukemia. 910-917.
  • Show author(s) 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.
  • Show author(s) 2012. Re: Murine double minute 2 promoter SNP309 polymorphism and prostate cancer risk: a meta-analysis. International journal of urology. 966-966.
  • Show author(s) 2012. P53 and its molecular basis to chemoresistance in breast cancer. Expert opinion on therapeutic targets. S23-S30.
  • Show author(s) 2012. MDM2 Promoter SNP344T>A (rs1196333) Status Does Not Affect Cancer Risk. PLOS ONE. 6 pages.
  • Show author(s) 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 pages.
  • Show author(s) 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.
  • Show author(s) 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 pages.
  • Show author(s) 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.
  • Show author(s) 2012. Correlation analysis of p53 protein isoforms with NPM1/FLT3 mutations and therapy response in acute myeloid leukemia. Oncogene. 1533-1545.
  • Show author(s) 2012. Chemosensitivity and p53; new tricks by an old dog. Breast Cancer Research. 325.
  • Show author(s) 2011. The nuclear receptor coactivator PELP1/MNAR is positively correlated with estrogen levels in breast cancer patients.
  • Show author(s) 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.
  • Show author(s) 2011. Recent data on intratumor estrogens in breast cancer. Steroids. 786-791.
  • Show author(s) 2011. RINF (CXXC5) is overexpressed in solid tumors and is an unfavorable prognostic factor in breast cancer(dagger). Annals of Oncology. 2208-2215.
  • Show author(s) 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 pages.
  • Show author(s) 2011. MDM2 promoter SNP285 and SNP309; phylogeny and impact on cancer risk. OncoTarget. 251-258.
  • Show author(s) 2011. Exploring breast cancer estrogen disposition: The basis for endocrine manipulation. Clinical Cancer Research. 4948-4958.
  • Show author(s) 2011. Effects of the MDM2 promoter SNP285 and SNP309 on Sp1 transcription factor binding and cancer risk. Transcription.
  • Show author(s) 2011. Clinical effect of Temozolomide-based chemotherapy in poorly differentiated endocrine carcinoma after progression on first-line chemotherapy. Cancer. 4617-4622.
  • Show author(s) 2011. Alterations of the retinoblastoma gene in metastatic breast cancer. Clinical and Experimental Metastasis. 319-326.
  • Show author(s) 2010. Spontaneous Malignant Transformation of Human Mesenchymal Stem Cells Reflects Cross-Contamination: Putting the Research Field on Track - Letter. Cancer Research. 6393-6396.
  • Show author(s) 2010. Identification and characterization of retinoblastoma gene mutations disturbing apoptosis in human breast cancers. Molecular Cancer. 13 pages.
  • Show author(s) 2010. Gene Expression Profiling-Based Identification of Molecular Subtypes in Stage IV Melanomas with Different Clinical Outcome. Clinical Cancer Research. 3356-3367.
  • Show author(s) 2010. Epidermal growth factor receptors (ErbB/HER) and the ligand Neuregulin 1 (NRG1) increase in breast tumors during short time treatment with aromatase inhibitors.
  • Show author(s) 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.
  • Show author(s) 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 pages.
  • Show author(s) 2007. UTRech tm: Exploiting mRNA Targeting To Increase Protein Secetion From Mammalian Cells. 8 pages.
  • Show author(s) 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.
  • Show author(s) 2007. The MDM2 SNP309 G/T promoter polymorphism is associated with chemoresistance in primary breast cancers harbouring mutations in the TP53 gene.
  • Show author(s) 2007. P21/waf1 mutation and drug resistance to paclitaxel in locally advanced breast cancer. International Journal of Cancer. 2749-2749.
  • Show author(s) 2007. Mutations and polymorphisms of the p21B transcript in breast cancer. International Journal of Cancer. 908-910.
  • Show author(s) 2007. Germline Genetic Alterations Affecting CDKN2A, MDM2 and CDKN1A in Melanoma and Breast Cancer Patients.
  • Show author(s) 2007. Breast cancer prognostication and prediction in the postgenomic era. Annals of Oncology. 1293-1306.
  • Show author(s) 2007. Adjuvant treatment: the contribution of expression microarrays. Breast Cancer Research.
  • Show author(s) 2006. The novel p21 polymorphism p21(G251A) is associated with locally advanced breast cancer. Clinical Cancer Research. 6000-6004.
  • Show author(s) 2006. Functional characterisation of novel p53 mutants.
  • Show author(s) 2006. A novel type of deletion in the CDKN2A gene identified in a melanoma-prone family. Genes, Chromosomes and Cancer. 1155-1163.
  • Show author(s) 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.

More information in national current research information system (CRIStin)

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

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

 

Nowegian Cancer Genomics Consotrium (NCGC)

http://kreftgenomikk.no/en/