Drs Sigrid Marie Kraggerud, Christina Høi-Hansen and Sharmini Alagaratnam publish in Endrocrine Reviews

From left: Kraggerud, Hři-Hansen and Alagaratnam

In a comprehensive review the Lothe group together with colleagues from University of Copenhagen (Rigshospitalet), Dr. Ewa Rajpert-Dde Meyts group, revisit the total literature on molecular biology of germ cell tumors of the ovary.
Endrocrine Reviews is the highest ranked journal in the category of Endocrinology and metabolism with impact factor of 19.9.

The molecular features of the malignant Ovarian Germ Cell Tumors (mOGCTs) underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors.

The common ovarian cancers arise from the surface epithelium whereas the ovarian germ cell tumors (OGCT) arise from cellular elements of the follicle. This review deals with the malignant OGCTs which arise predominantly in girls and young women with a peak incidence between 15 and 20 years of age. Given the presumed common cell of origin in mOGCT and their male counterpart, testicular GCT, parallels between the molecular mechanisms of these two tumor types are discussed from the perspective of development, endocrinological influences and pathogenesis. The mOGCTs are believed to be derived from PGCs, where the pluripotency traits they retain facilitate the potential to differentiate into the spectrum of histological subtypes. The development of non-dysgerminomas is characterized by differentiation of these cells into histologies that mimic embryonic and extraembryonic tissues. From a complete literature survey molecular characteristics of these tumors (providing a reference list of 340 papers) are presented. The GCTs rarely contain mutations in known oncogenes or tumor suppressor genes showing that the pathogenesis of GCT differs from somatic tumor development, possibly by exploiting the retained pluripotency and the primed demethylation process of the PGC. The aberrant genomes and transcriptomes of mOGCT show differential involvement of the WNT and TGF-b signalling cascades among the various subtypes.

Dr Sigrid Marie Kraggerud is funded as a researcher by South- Eastern Norway Regional Health Authority (HSØ) and is studying normal genetic variation in patients with testicular germ cell tumor as risk factors to develop disease and in relation to long term side effects from chemotherapy.


Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison With Testicular Counterparts: Implications for Pathogenesis.
Kraggerud SM, Hoei-Hansen CE, Alagaratnam S, Skotheim RI, Abeler VM, Rajpert-De Meyts E, Lothe RA.
Endocr Rev. 2013 Apr 10.

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