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  • Betancourt, Lazaro HiramLund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups (author)

The hidden story of heterogeneous B-raf V600E mutation quantitative protein expression in metastatic melanoma—association with clinical outcome and tumor phenotypes

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-12-09
  • MDPI AG,2019

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:7ac9c379-b138-4d81-b091-2904ee862047
  • https://lup.lub.lu.se/record/7ac9c379-b138-4d81-b091-2904ee862047URI
  • https://doi.org/10.3390/cancers11121981DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:142709428URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas clearly reveal the existence of inter-and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression in the mutated protein is associated with a more aggressive tumor progression. Our study design, comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis, may enable the eventual delineation of patient responders/non-responders and subsequent therapy for malignant melanoma.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Szasz, A. MarcellLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,Semmelweis University(Swepub:lu)ma4462sz (author)
  • Kuras, MagdalenaLund University,Lunds universitet,Masspektrometri,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Mass Spectrometry,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)ma4830ku (author)
  • Murillo, Jimmy RodriguezKarolinska Institute (author)
  • Sugihara, YutakaKarolinska Institute(Swepub:lu)med-yas (author)
  • Pla, IndiraLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Protein Science and Imaging,Clinical Chemistry, Malmö,Lund University Research Groups,Skåne University Hospital(Swepub:lu)in2411pl (author)
  • Horvath, ZsoltLund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)zs8836ho (author)
  • Pawłowski, KrzysztofLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Protein Science and Imaging,Clinical Chemistry, Malmö,Lund University Research Groups,Warsaw University of Life Sciences,Skåne University Hospital(Swepub:lu)med-kzp (author)
  • Rezeli, MelindaLund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)elma-mrl (author)
  • Miharada, KenichiLund University,Lunds universitet,Stamcellsmetabolism,Forskargrupper vid Lunds universitet,Stem Cell Metabolism,Lund University Research Groups(Swepub:lu)med-kmh (author)
  • Gil, JeovanisLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)je2062gi (author)
  • Eriksson, JonatanLund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)jo5130er (author)
  • Appelqvist, RogerLund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)elma-rai (author)
  • Miliotis, TassoAstraZeneca, Sweden(Swepub:lu)med-tms (author)
  • Baldetorp, BoLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-bba (author)
  • Ingvar, ChristianLund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Lund Melanoma Study Group,Lund University Research Groups,Skåne University Hospital(Swepub:lu)kir-cin (author)
  • Olsson, HåkanLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Melanoma Study Group,Lund University Research Groups(Swepub:lu)onk-hol (author)
  • Lundgren, LottaLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-ilu (author)
  • Horvatovich, PeterUniversity of Groningen(Swepub:lu)pe4034ho (author)
  • Welinder, CharlotteLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,CEBMMS PI,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups(Swepub:lu)onk-cbr (author)
  • Wieslander, ElisabetLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups(Swepub:lu)med-etw (author)
  • Kwon, Ho JeongYonsei University(Swepub:lu)ho7625kw (author)
  • Malm, JohanLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Protein Science and Imaging,Clinical Chemistry, Malmö,Lund University Research Groups,Skåne University Hospital(Swepub:lu)klke-jma (author)
  • Nemeth, Istvan BalazsUniversity of Szeged (author)
  • Jönsson, GöranLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Melanoma Study Group,Lund University Research Groups(Swepub:lu)onk-gjo (author)
  • Fenyö, DavidNew York University (author)
  • Sanchez, AnielLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Protein Science and Imaging,Clinical Chemistry, Malmö,Lund University Research Groups,Skåne University Hospital(Swepub:lu)an3128sa (author)
  • Marko-Varga, GyörgyLund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)akem-gmv (author)
  • Clinical Protein Science and ImagingForskargrupper vid Lunds universitet (creator_code:org_t)

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  • In:Cancers: MDPI AG11:122072-6694

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