Ovarian dysgerminomas are characterised by frequent <it>KIT </it>mutations and abundant expression of pluripotency markers

<p>Abstract</p> <p>Background</p> <p>Ovarian germ cell tumours (OGCTs) typically arise in young females and their pathogenesis remains poorly understood. We investigated the origin of malignant OGCTs and underlying molecular events in the development of the various hist...

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Main Authors: Kærn Janne, Abeler Vera M, Kraggerud Sigrid M, Hoei-Hansen Christina E, Rajpert-De Meyts Ewa, Lothe Ragnhild A
Format: Article
Language:English
Published: BMC 2007-02-01
Series:Molecular Cancer
Online Access:http://www.molecular-cancer.com/content/6/1/12
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spelling doaj-913d2e01a35347d6b914e76ad2d472412020-11-24T21:49:57ZengBMCMolecular Cancer1476-45982007-02-01611210.1186/1476-4598-6-12Ovarian dysgerminomas are characterised by frequent <it>KIT </it>mutations and abundant expression of pluripotency markersKærn JanneAbeler Vera MKraggerud Sigrid MHoei-Hansen Christina ERajpert-De Meyts EwaLothe Ragnhild A<p>Abstract</p> <p>Background</p> <p>Ovarian germ cell tumours (OGCTs) typically arise in young females and their pathogenesis remains poorly understood. We investigated the origin of malignant OGCTs and underlying molecular events in the development of the various histological subtypes of this neoplasia.</p> <p>Results</p> <p>We examined <it>in situ </it>expression of stem cell-related (NANOG, OCT-3/4, KIT, AP-2γ) and germ cell-specific proteins (MAGE-A4, NY-ESO-1, TSPY) using a tissue microarray consisting of 60 OGCT tissue samples and eight ovarian small cell carcinoma samples. Developmental pattern of expression of NANOG, TSPY, NY-ESO-1 and MAGE-A4 was determined in foetal ovaries (gestational weeks 13–40). The molecular genetic part of our study included search for the presence of Y-chromosome material by fluorescence <it>in situ </it>hybridisation (FISH), and mutational analysis of the <it>KIT </it>oncogene (exon 17, codon 816), which is often mutated in testicular GCTs, in a subset of tumour DNA samples. We detected a high expression of transcription factors related to the embryonic stem cell-like pluripotency and undifferentiated state in OGCTs, but not in small cell carcinomas, supporting the view that the latter do not arise from a germ cell progenitor. Bilateral OGCTs expressed more stem cell markers than unilateral cases. However, <it>KIT </it>was mutated in 5/13 unilateral dysgerminomas, whereas all bilateral dysgerminomas (n = 4) and all other histological types (n = 22) showed a wild type sequence. Furthermore, tissue from five phenotypic female patients harbouring combined dysgerminoma/gonadoblastoma expressed TSPY and contained Y-chromosome material as confirmed by FISH.</p> <p>Conclusion</p> <p>This study provides new data supporting two distinct but overlapping pathways in OGCT development; one involving spontaneous <it>KIT </it>mutation(s) leading to increased survival and proliferation of undifferentiated oogonia, the other related to presence of Y chromosome material and ensuing gonadal dysgenesis in phenotypic females.</p> http://www.molecular-cancer.com/content/6/1/12
collection DOAJ
language English
format Article
sources DOAJ
author Kærn Janne
Abeler Vera M
Kraggerud Sigrid M
Hoei-Hansen Christina E
Rajpert-De Meyts Ewa
Lothe Ragnhild A
spellingShingle Kærn Janne
Abeler Vera M
Kraggerud Sigrid M
Hoei-Hansen Christina E
Rajpert-De Meyts Ewa
Lothe Ragnhild A
Ovarian dysgerminomas are characterised by frequent <it>KIT </it>mutations and abundant expression of pluripotency markers
Molecular Cancer
author_facet Kærn Janne
Abeler Vera M
Kraggerud Sigrid M
Hoei-Hansen Christina E
Rajpert-De Meyts Ewa
Lothe Ragnhild A
author_sort Kærn Janne
title Ovarian dysgerminomas are characterised by frequent <it>KIT </it>mutations and abundant expression of pluripotency markers
title_short Ovarian dysgerminomas are characterised by frequent <it>KIT </it>mutations and abundant expression of pluripotency markers
title_full Ovarian dysgerminomas are characterised by frequent <it>KIT </it>mutations and abundant expression of pluripotency markers
title_fullStr Ovarian dysgerminomas are characterised by frequent <it>KIT </it>mutations and abundant expression of pluripotency markers
title_full_unstemmed Ovarian dysgerminomas are characterised by frequent <it>KIT </it>mutations and abundant expression of pluripotency markers
title_sort ovarian dysgerminomas are characterised by frequent <it>kit </it>mutations and abundant expression of pluripotency markers
publisher BMC
series Molecular Cancer
issn 1476-4598
publishDate 2007-02-01
description <p>Abstract</p> <p>Background</p> <p>Ovarian germ cell tumours (OGCTs) typically arise in young females and their pathogenesis remains poorly understood. We investigated the origin of malignant OGCTs and underlying molecular events in the development of the various histological subtypes of this neoplasia.</p> <p>Results</p> <p>We examined <it>in situ </it>expression of stem cell-related (NANOG, OCT-3/4, KIT, AP-2γ) and germ cell-specific proteins (MAGE-A4, NY-ESO-1, TSPY) using a tissue microarray consisting of 60 OGCT tissue samples and eight ovarian small cell carcinoma samples. Developmental pattern of expression of NANOG, TSPY, NY-ESO-1 and MAGE-A4 was determined in foetal ovaries (gestational weeks 13–40). The molecular genetic part of our study included search for the presence of Y-chromosome material by fluorescence <it>in situ </it>hybridisation (FISH), and mutational analysis of the <it>KIT </it>oncogene (exon 17, codon 816), which is often mutated in testicular GCTs, in a subset of tumour DNA samples. We detected a high expression of transcription factors related to the embryonic stem cell-like pluripotency and undifferentiated state in OGCTs, but not in small cell carcinomas, supporting the view that the latter do not arise from a germ cell progenitor. Bilateral OGCTs expressed more stem cell markers than unilateral cases. However, <it>KIT </it>was mutated in 5/13 unilateral dysgerminomas, whereas all bilateral dysgerminomas (n = 4) and all other histological types (n = 22) showed a wild type sequence. Furthermore, tissue from five phenotypic female patients harbouring combined dysgerminoma/gonadoblastoma expressed TSPY and contained Y-chromosome material as confirmed by FISH.</p> <p>Conclusion</p> <p>This study provides new data supporting two distinct but overlapping pathways in OGCT development; one involving spontaneous <it>KIT </it>mutation(s) leading to increased survival and proliferation of undifferentiated oogonia, the other related to presence of Y chromosome material and ensuing gonadal dysgenesis in phenotypic females.</p>
url http://www.molecular-cancer.com/content/6/1/12
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