- Stand van zaken

30 januari: Aan het herstellen van de operatie
Na een gelukte operatie (tumoren bleken beperkt tot milt, geen zichtbare uitzaaiingen) gevolgd door een bijzonder spannend weekend door plotseling opkomende koorts en een longontsteking (...) die adequaat werd getemperd door antibiotica, werden in de loop van maandag 20/1 alle drains, katheter en epiduraal verwijderd. Op donderdag 24/1 naar huis. En daar word ik nu al weer een week koninklijk verzorgd en vertroeteld door zusje, man en gezellige bezoekers. Veel in bed en af en toe een frisse neus. Meer is het niet, want dan krijg ik buikpijn.
Voorlopig geen chemo. Controle afspraak in het AVL op 6 maart. Tot die tijd rustig herstellen en conditie opbouwen. Het beste van dit al: ik leef in ieder geval nog! Want hoeveel keren kun je afscheid nemen en je voorbereiden op de dood?

13 januari: Bijna!
Afgelopen donderdag telefonisch de bevestiging voor 17/1 doorgekregen. Gezien mijn enorme verkoudheid van afgelopen 1,5 week was dat uitstel een geluk bij een ongeluk. Hoewel nog hoesterig en snotterig, loop ik weer elke dag buiten om te genieten van de frisse lucht.

Op 9/1 besloten om via de huisarts mijn tumormarker, de CA125, te laten meten: 28. Waarbij de doktersassistente blij uitriep: goed zo, onder de normaalwaarde! En dat met minimaal twee tumoren in mijn lijf... Goedbedoeld maar oer stom.

's Nachts droom ik van de operatie. Verder ben ik er bijna helemaal klaar voor. Mijn bureau raakt leger, ik zelf raak een beetje uit gecommuniceerd en verlang naar stilte en rust. Vooral verlang ik naar de periode na de operatie. Om mijn eigen leven weer op te pakken.

Rutger neemt de honneurs en communicatie waar, zusje is beschikbaar voor ondersteuning, liefde en zorg en dan moet ik nu doen waarin ik zo slecht ben: loslaten!

3 januari: Herziene planning operatie
Gisteren een mail ontvangen van het AVL dat ik sta ingepland voor 17 januari. We'll see. 
De gedachte om geheel van de operatie af te zien schiet mij dikwijls te binnen.
Dit afwachten in onzekerheid sinds 5 december vind ik geen kwaliteit van leven. Ik leef in grote onvrijheid daardoor. Gelukkig houden de vele fijne momenten thuis en met familie en vrienden mij op de been.
Update door d.d.
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- UT Health Science Center San Antonio Researcher Receives Grant to Fight Ovarian Cancer

http://bionews-tx.com/news/2014/01/27/ut-health-science-center-san-antonio-researcher-receives-grant-to-fight-ovarian-cancer/

ovarian cancerA researcher at the University of Texas Health Science Center at San Antonio is working on a new treatment for ovarian cancer by seeking a way to turn the body’s own defenses on the disease, one of the deadliest of all cancers.
Currently an immunologist at the UT Health Science Center, Dr. Tyler Curiel has received a $900,00 grant from the Ovarian Cancer Research Foundation in support for her research. Curiel’s group will develop a multi-modal immune therapy for ovarian cancer using approaches in three key areas: first, they will reduce immune impediments to effective ovarian cancer immunotherapy; the team will then block molecular mechanisms that drive tumor growth and inhibit anti-tumor immunity; finally, they use new-generation adoptive T cell (a type of lymphocyte that plays a central role in cell-mediated immunity) transfers.
Curiel is also a professor at the Health Science Center’s School of Medicine. He has won a separate grant has been selected to participate in an ambitious multimillion-dollar international effort to develop a new drug that could be used to fight an array of cancers.

His current program has three highly integrated and interactive projects, led by four ovarian cancer thought leaders, who will work to identify optimal approaches in these three key areas and means to combine them for maximal clinical effects.
“Our program will allow development of a major grant to test approaches clinically, first in resistant cancers, and later in relapse prevention and as treatment after failure of front-line therapy,” Curiel said.
Update door d.d.
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- Integrated analysis of germline and somatic variants in ovarian cancer

http://www.nature.com/ncomms/2014/140122/ncomms4156/full/ncomms4156.html
:


  • Krishna L. Kanchi,
  • Kimberly J. Johnson,
  • Charles Lu,
  • Michael D. McLellan,
  • Mark D. M. Leiserson,
  • Michael C. Wendl,
  • Qunyuan Zhang,
  • Daniel C. Koboldt,
  • Mingchao Xie,
  • Cyriac Kandoth,
  • Joshua F. McMichael,
  • Matthew A. Wyczalkowski,
  • David E. Larson,
  • Heather K. Schmidt,
  • Christopher A. Miller,
  • Robert S. Fulton,
  • Paul T. Spellman,
  • Elaine R. Mardis,
  • Todd E. Druley,
  • Timothy A. Graubert

    • Nature Communications
     
    5,
     
    Article number:
     
    3156
     
    doi:10.1038/ncomms4156
    Received
     
    Accepted
     
    Published
     

    Abstract



    We report the first large-scale exome-wide analysis of the combined germline–somatic landscape in ovarian cancer. Here we analyse germline and somatic alterations in 429 ovarian carcinoma cases and 557 controls. We identify 3,635 high confidence, rare truncation and 22,953 missense variants with predicted functional impact. We find germline truncation variants and large deletions across Fanconi pathway genes in 20% of cases. Enrichment of rare truncations is shown in BRCA1, BRCA2 and PALB2. In addition, we observe germline truncation variants in genes not previously associated with ovarian cancer susceptibility (NF1, MAP3K4, CDKN2B and MLL3). Evidence for loss of heterozygosity was found in 100 and 76% of cases with germline BRCA1 and BRCA2truncations, respectively. Germline–somatic interaction analysis combined with extensive bioinformatics annotation identifies 222 candidate functional germline truncation and missense variants, including two pathogenic BRCA1 and 1 TP53 deleterious variants. Finally, integrated analyses of germline and somatic variants identify significantly altered pathways, including the Fanconi, MAPK and MLL pathways.

    Subject terms:

    At a glance

    Figures

    First | 1-4 of 5 | Last
    left
    1. Overview of the integrated analysis of germline and somatic variants in 429 TCGA serous ovarian cases.
      Figure 1
    2. Germline copy-number variants in BRCA1.
      Figure 2
    3. Lolliplots showing the distribution of germline truncation variants and somatic mutations.
      Figure 3
    4. LOH analysis in tumour samples.
      Figure 4
    5. Significant pathways and subnetworks in ovarian cancer.
      Figure 5
    right

    References



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    Download references

    Author information



    1. These authors contributed equally to this work

      • Krishna L. Kanchi, 
      • Kimberly J. Johnson & 
      • Charles Lu

    Affiliations

    1. The Genome Institute, Washington University, St. Louis, Missouri 63108, USA

      • Krishna L. Kanchi,
        •  
      • Kimberly J. Johnson,
        •  
      • Charles Lu,
        •  
      • Michael D. McLellan,
        •  
      • Michael C. Wendl,
      • Qunyuan Zhang,
        •  
      • Daniel C. Koboldt,
        •  
      • Mingchao Xie,
        •  
      • Cyriac Kandoth,
        •  
      • Joshua F. McMichael,
        •  
      • Matthew A. Wyczalkowski,
        •  
      • David E. Larson,
        •  
      • Heather K. Schmidt,
        •  
      • Christopher A. Miller,
        •  
      • Robert S. Fulton,
      • Elaine R. Mardis,
        •  
      • Richard K. Wilson &
        •  
      • Li Ding

    2. Brown School, Washington University, St. Louis, Missouri 63130, USA

      • Kimberly J. Johnson

    3. Oregon Health and Science University, Portland, Oregon 97239, USA

      • Kimberly J. Johnson &
        •  
      • Paul T. Spellman

    4. Department of Computer Science, Brown University, Providence, Rhode Island 02912, USA

      • Mark D. M. Leiserson &
        •  
      • Benjamin J. Raphael

    5. Department of Genetics, Washington University, St. Louis, Missouri 63108, USA

      • Michael C. Wendl,
        •  
      • Qunyuan Zhang,
        •  
      • David E. Larson,
        •  
      • Robert S. Fulton,
        •  
      • Elaine R. Mardis,
        •  
      • Todd E. Druley,
        •  
      • Richard K. Wilson &
        •  
      • Li Ding

    6. Department of Mathematics, Washington University, St. Louis, Missouri 63108, USA

      • Michael C. Wendl

    7. Siteman Cancer Center, Washington University, St. Louis, Missouri 63108, USA

      • Elaine R. Mardis,
        •  
      • Timothy A. Graubert,
        •  
      • Richard K. Wilson &
        •  
      • Li Ding

    8. Department of Pediatrics, Washington University, St. Louis, Missouri 63108, USA

      • Todd E. Druley

    9. Department of Medicine, Washington University, St. Louis, Missouri 63108, USA

      • Timothy A. Graubert &
        •  
      • Li Ding

    10. The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA

      • Paul J. Goodfellow

    Contributions

    L.D. and R.K.W. jointly supervised research. L.D., K.L.K., K.J.J., C.L., M.D.M., M.D.M.L., C.K., M.A.W., J.F.M., D.C.K., C.A.M., P.T.S. and B.J.R. analysed the data. M.C.W. and Q.Z. performed statistical analysis. K.L.K., C.L., J.F.M., M.D.M., M.A.W. and L.D. prepared figures and tables. R.S.F. performed experiments. E.R.M. and D.E.L. contributed analysis tools. L.D., K.J.J., T.A.G., P.J.G., T.E.D. and B.J.R conceived and designed the experiments. L.D. and K.J.J. wrote the manuscript. K.L.K., K.J.J., C.L. and M.D.M. contributed equally but due to restrictions on the number of first authors only K.L.K., K.J.J. and C.L. are denoted as such.

    Competing financial interests

    The authors declare no competing financial interests.

    Corresponding author

    Correspondence to: 

    Supplementary information



    PDF files

    1. Supplementary Figures and Tables (660 KB)
      Supplementary Figures S1-S5 and Supplementary Tables S1-S5

    Excel files

    1. Supplementary Data 1 (39 KB)
      Clinical Information For 557 WHI Cases
    2. Supplementary Data 2 (21 KB)
      429 TCGA Ovarian Cases Data Types and Clinical Information
    3. Supplementary Data 3 (3,642 KB)
      Somatic Mutations in 429 TCGA Ovarian cases
    4. Supplementary Data 4 (466 KB)
      All 3,635 high confidence, rare (<1% population variant allele frequency) germline truncations including 115 validated germline truncations in cancer
    5. Supplementary Data 5 (9 KB)
      Validated Truncation Variants in Cancer Genes
    6. Supplementary Data 6 (2,691 KB)
      All 22,953 missense variants (<1% population variant allele frequency), predicted to be functional by Condel in 387 Caucasians
    7. Supplementary Data 7 (575 KB)
      All truncation variants (<1% population variant allele frequency), in 557 Caucasians
    8. Supplementary Data 8 (2,434 KB)
      All 30335 missense variants (<1% population variant allele frequency), predicted to be functional by Condel in 557 Caucasians
    9. Supplementary Data 9 (331 KB)
      Burden Analysis results for the Missense variants
    10. Supplementary Data 10 (16 KB)
      Burden Analysis Results for the Missense and Truncation Variants in Cancer Genes
    11. Supplementary Data 11 (13 KB)
      Germline truncation and missense within close proximity (5 amino acid) to COSMIC/OMIM variants
    12. Supplementary Data 12 (67 KB)
      Germline truncations display LOH in corresponding tumor
    13. Supplementary Data 13 (14 KB)
      Germline missense variants in cancer genes display LOH in corresponding tumor
    14. Supplementary Data 14 (21 KB)
      High confidence, functional truncation and missense variants identified by integrated approaches
    15. Supplementary Data 15 (21 KB)
      Significant pathways identified by PathScan using germline truncations and somatic mutations
    16. Supplementary Data 16 (8 KB)
      Four significant subnetworks identified by HotNet using germline truncations and somatic mutations (P = 0.17)
    17. Supplementary Data 17 (17 KB)
      672 cancer genes
    18. Supplementary Data 18 (36 KB)
      Validated Missense Variants using 11 Whole Genome Sequencing BAMs
    19. Supplementary Data 19 (12 KB)
      Primers for TCGA Germline Validation using 3730 sequencing platform
    20. Supplementary Data 20 (49 KB)
      Primers for TCGA Germline Validation using miseq
    Update door d.d.
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