Department of Pathology

1
Comparative genetics (testicular GCTs) clinical
implications.
Leendert Looijenga
Department of Pathology JNI-Daniel den Hoed
Cancer Center
ESMO-EIS meeting, Munich, Germany, May 15, 2008
(Biology of GCTs)
2
Levels of Comparative genetics
Department of Pathology JNI-Daniel den Hoed
Cancer Center
TYPE II (TESTICULAR) GCTS
Histology biology type I (TE/YST) type
II (SE/NS) type III (SS)
Integrated analysis datasets
3
Levels of clinical implication
Type II GCTs
I. DIAGNOSIS
II. PROGNOSIS
III. PREDICTION
PATHO-BIOLOGY
Department of Pathology JNI-Daniel den Hoed
Cancer Center
Defined set of characteristics
Question Intrinsic or Pathogenetic??
4
Clinical implication I. Diagnosis (A)
Expression 9p genes
Department of Pathology JNI-Daniel den Hoed
Cancer Center
Looijenga et al. 2006
5
Clinical implication I Diagnosis (B)
Department of Pathology JNI-Daniel den Hoed
Cancer Center
De Jong et al., 2008 Looijenga et al., 2008
Korkola et al., 2008.
6
Clinical implication I/II. Diagn./Progn.
Rapley et al., 2004 McIntyre et al., 2005
Department of Pathology JNI-Daniel den Hoed
Cancer Center
No target resistant GCTs (Mayer et al. Cancer
2003) Protein kinases not frequently
mutated (Stephens et al.,
GCC, 2005)
Technical
Biological
Heterogeneous results in different series
Stoop et al., J. Pathol. 2008 in press
7
Clinical implication II/III. Progn./pred.
Department of Pathology JNI-Daniel den Hoed
Cancer Center
Plt0.0001
Mayer et al., 2002 Valesco et al., 2004/7 (gtrate
of relapse)
IHC hMLH1-PMS2 (p0.02) hMSH2, hMSH6
(plt0.0001)
Patients 35 refractory (1 alive) (11
extragon./6 late relapses)
IHC hMLH1, PMS2 (hMutLa) hMSH2, hMSH6 (hMutSa)
MSI D2S123,D5S346,D17S250, BAT40/MSH6, BAT25,
BAT26
8
Biological and possible clinical implication
Oncogene (RAS) HTERT P53-RB
Albanell et al., 1999 Schrader et al., 2002
Cressey et al. , 2002 Schrader et al., 2002
Lopatina et al., 2003
Department of Pathology JNI-Daniel den Hoed
Cancer Center
Voorhoeve et al., Cell 2006 Gillis et al., J
Pathol 2007
9
EIS meeting take home messages
Histology
Clinical behavior
Improvements
Germ cell biology (embryogenesis)
Diagnosis
Pathogenesis
Department of Pathology JNI-Daniel den Hoed
Cancer Center
Prognosis
Prediction
10
Acknowledgements
Erasmus MC, NL Pathology Ad Gillis, Ruud van
Gurp, Hans Stoop, Jeroen de Jong, Remko Hersmus,
Hendrik Wermann, Bertie de Leeuw, Martine
Cools, Wolter Oosterhuis Department of
Bioinformatics Peter vd Spek Andrology/Urology
Gert Dohle, Wim Kirkels, Rob Weber, Katja
Wolffenbuttel, Chris Bangma Dept. Human Genetics,
UMCN, NL Joris Veltman, Eric Schoenmakers, Ad
Geurts Van Kessel Department of Genetics,
Cell Biology and Develop- ment, University of
Minnesota, Minneapolis, USA David Zarkower,
Vivian Bardell Departm. Oncology, Hamburg,
G Friedemann Honecker, Carsten Bokemeyer Cell
Biology, NKI, NL Mathijs Voorhoeve, Reuven Agami
Department of Pediatric Oncology, Dortmund,
G Dominik Schneider Department of Medicine, San
Fransisco, USA Yun-Fai Chris Lau, Yunmin
Li
Rev. Fund, ESMO, ESPE, ZonMw-NWO, Deutsche
KrebsHilfe, EORTC, Dr. Mildred Scheel
Foundation,
Department of Pathology JNI-Daniel den Hoed
Cancer Center
Integromics Pedro de Alarcon Applied
Biosystems/Applera Jon Sherlock, Astrid
Ferlinz, John Baeten, Van Lam, Yongmin Sun,
Bianca Hesselius, David Howells, Katheen
Shelton, Richard Henfrey
Urologists and Pathologists