The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform
William D Foulkes - One of the best experts on this subject based on the ideXlab platform.
-
no small surprise small cell carcinoma of the ovary hypercalcaemic type is a Malignant Rhabdoid Tumour
The Journal of Pathology, 2014Co-Authors: William D Foulkes, Blaise A Clarke, Martin Hasselblatt, Jacek Majewski, Steffen Albrecht, Glenn W MccluggageAbstract:Whole-exome sequencing (WES) is revolutionizing medical diagnostics and taxonomy. In less than 5 years since its first use, WES has revealed unexpected molecular drivers of numerous cancers. Here, we describe our use of WES to uncover the true nature of an enigmatic pathological entity, small-cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), which has resisted definitive characterisation since it was first described in 1979. We conducted WES using three families with SCCOHT and identified deleterious mutations in the chromatin-remodelling gene SMARCA4 (encoding BRG1) in all cases. Follow-up of these findings, using both Sanger sequencing and WES of formalin-fixed paraffin-embedded Tumours, showed that virtually all SCCOHTs we studied lacked functional SMARCA4/BRG1. Notably, this gene, and the related SMARCB1 gene, is mutated in most, if not all, atypical teratoid/Rhabdoid Tumours and Malignant Rhabdoid Tumours. Other groups have similar findings. We review the relationship between these three neoplasms, discuss how they were distinguished from morphologically similar neoplasms, consider their similarities and show how WES has revealed that SCCOHTs are in fact Rhabdoid Tumours. We propose that SCCOHT be renamed ‘Malignant Rhabdoid Tumour of the ovary’ (MRTO) to reflect these observations. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
-
No small surprise – small cell carcinoma of the ovary, hypercalcaemic type, is a Malignant Rhabdoid Tumour
The Journal of Pathology, 2014Co-Authors: William D Foulkes, Blaise A Clarke, Martin Hasselblatt, Jacek Majewski, Steffen Albrecht, W. Glenn MccluggageAbstract:Whole-exome sequencing (WES) is revolutionizing medical diagnostics and taxonomy. In less than 5 years since its first use, WES has revealed unexpected molecular drivers of numerous cancers. Here, we describe our use of WES to uncover the true nature of an enigmatic pathological entity, small-cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), which has resisted definitive characterisation since it was first described in 1979. We conducted WES using three families with SCCOHT and identified deleterious mutations in the chromatin-remodelling gene SMARCA4 (encoding BRG1) in all cases. Follow-up of these findings, using both Sanger sequencing and WES of formalin-fixed paraffin-embedded Tumours, showed that virtually all SCCOHTs we studied lacked functional SMARCA4/BRG1. Notably, this gene, and the related SMARCB1 gene, is mutated in most, if not all, atypical teratoid/Rhabdoid Tumours and Malignant Rhabdoid Tumours. Other groups have similar findings. We review the relationship between these three neoplasms, discuss how they were distinguished from morphologically similar neoplasms, consider their similarities and show how WES has revealed that SCCOHTs are in fact Rhabdoid Tumours. We propose that SCCOHT be renamed ‘Malignant Rhabdoid Tumour of the ovary’ (MRTO) to reflect these observations. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Glenn W Mccluggage - One of the best experts on this subject based on the ideXlab platform.
-
no small surprise small cell carcinoma of the ovary hypercalcaemic type is a Malignant Rhabdoid Tumour
The Journal of Pathology, 2014Co-Authors: William D Foulkes, Blaise A Clarke, Martin Hasselblatt, Jacek Majewski, Steffen Albrecht, Glenn W MccluggageAbstract:Whole-exome sequencing (WES) is revolutionizing medical diagnostics and taxonomy. In less than 5 years since its first use, WES has revealed unexpected molecular drivers of numerous cancers. Here, we describe our use of WES to uncover the true nature of an enigmatic pathological entity, small-cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), which has resisted definitive characterisation since it was first described in 1979. We conducted WES using three families with SCCOHT and identified deleterious mutations in the chromatin-remodelling gene SMARCA4 (encoding BRG1) in all cases. Follow-up of these findings, using both Sanger sequencing and WES of formalin-fixed paraffin-embedded Tumours, showed that virtually all SCCOHTs we studied lacked functional SMARCA4/BRG1. Notably, this gene, and the related SMARCB1 gene, is mutated in most, if not all, atypical teratoid/Rhabdoid Tumours and Malignant Rhabdoid Tumours. Other groups have similar findings. We review the relationship between these three neoplasms, discuss how they were distinguished from morphologically similar neoplasms, consider their similarities and show how WES has revealed that SCCOHTs are in fact Rhabdoid Tumours. We propose that SCCOHT be renamed ‘Malignant Rhabdoid Tumour of the ovary’ (MRTO) to reflect these observations. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Giovanni Martinelli - One of the best experts on this subject based on the ideXlab platform.
-
Malignant Rhabdoid Tumour of the uterus an immunohistochemical and ultrastructural study
Virchows Archiv, 1992Co-Authors: M G Cattani, Giuseppe Viale, D Santini, Giovanni MartinelliAbstract:Malignant Rhabdoid Tumours (MRTs) are highly aggressive neoplasms which most frequently occur in the kidney of young children. Several cases of primary MRT occurring in extra-renal sites have been reported, particularly in the soft tissues. We report a case of primary MRT of the uterus, a very rare site for this neoplasm, with morphological, immunohistochemical and ultrastructural features corresponding to restrictive morphological criteria for MRT. The possible differential diagnoses were considered.
Nicholas K Foreman - One of the best experts on this subject based on the ideXlab platform.
-
congenital Malignant Rhabdoid Tumour of the gum margin
Oral Oncology, 1997Co-Authors: B L Pizer, M Ashworth, P J Berry, Nicholas K ForemanAbstract:The case of an infant born with a large polypoid Tumour arising from the mouth is described. The Tumour had the histological, immunohistochemical and ultrastructural phenotype of an extrarenal Malignant Rhabdoid Tumour and followed an aggressive clinical course. This is one of the few reported cases of Malignant Rhabdoid Tumour to present at birth. The oral Tumour was associated with a mass in the posterior cranial fossa. This was most likely to be a simultaneous second primary Tumour.
Steffen Albrecht - One of the best experts on this subject based on the ideXlab platform.
-
no small surprise small cell carcinoma of the ovary hypercalcaemic type is a Malignant Rhabdoid Tumour
The Journal of Pathology, 2014Co-Authors: William D Foulkes, Blaise A Clarke, Martin Hasselblatt, Jacek Majewski, Steffen Albrecht, Glenn W MccluggageAbstract:Whole-exome sequencing (WES) is revolutionizing medical diagnostics and taxonomy. In less than 5 years since its first use, WES has revealed unexpected molecular drivers of numerous cancers. Here, we describe our use of WES to uncover the true nature of an enigmatic pathological entity, small-cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), which has resisted definitive characterisation since it was first described in 1979. We conducted WES using three families with SCCOHT and identified deleterious mutations in the chromatin-remodelling gene SMARCA4 (encoding BRG1) in all cases. Follow-up of these findings, using both Sanger sequencing and WES of formalin-fixed paraffin-embedded Tumours, showed that virtually all SCCOHTs we studied lacked functional SMARCA4/BRG1. Notably, this gene, and the related SMARCB1 gene, is mutated in most, if not all, atypical teratoid/Rhabdoid Tumours and Malignant Rhabdoid Tumours. Other groups have similar findings. We review the relationship between these three neoplasms, discuss how they were distinguished from morphologically similar neoplasms, consider their similarities and show how WES has revealed that SCCOHTs are in fact Rhabdoid Tumours. We propose that SCCOHT be renamed ‘Malignant Rhabdoid Tumour of the ovary’ (MRTO) to reflect these observations. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
-
No small surprise – small cell carcinoma of the ovary, hypercalcaemic type, is a Malignant Rhabdoid Tumour
The Journal of Pathology, 2014Co-Authors: William D Foulkes, Blaise A Clarke, Martin Hasselblatt, Jacek Majewski, Steffen Albrecht, W. Glenn MccluggageAbstract:Whole-exome sequencing (WES) is revolutionizing medical diagnostics and taxonomy. In less than 5 years since its first use, WES has revealed unexpected molecular drivers of numerous cancers. Here, we describe our use of WES to uncover the true nature of an enigmatic pathological entity, small-cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), which has resisted definitive characterisation since it was first described in 1979. We conducted WES using three families with SCCOHT and identified deleterious mutations in the chromatin-remodelling gene SMARCA4 (encoding BRG1) in all cases. Follow-up of these findings, using both Sanger sequencing and WES of formalin-fixed paraffin-embedded Tumours, showed that virtually all SCCOHTs we studied lacked functional SMARCA4/BRG1. Notably, this gene, and the related SMARCB1 gene, is mutated in most, if not all, atypical teratoid/Rhabdoid Tumours and Malignant Rhabdoid Tumours. Other groups have similar findings. We review the relationship between these three neoplasms, discuss how they were distinguished from morphologically similar neoplasms, consider their similarities and show how WES has revealed that SCCOHTs are in fact Rhabdoid Tumours. We propose that SCCOHT be renamed ‘Malignant Rhabdoid Tumour of the ovary’ (MRTO) to reflect these observations. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
-
Familial Rhabdoid Tumour 'avant la lettre'—from pathology review to exome sequencing and back again
The Journal of Pathology, 2013Co-Authors: Leora Witkowski, Steffen Albrecht, Emilie Lalonde, Jian Zhang, Nancy Hamel, Luca Cavallone, James Nicholson, Nicholas Coleman, Matthew J. MurrayAbstract:Here we provide compelling evidence that next-generation sequencing will revolutionize diagnostics. We reappraised a case from 1991, published in 1993, describing the unique occurrence of an ovarian immature teratoma arising in a young woman and a clonally distinct intracerebral immature teratoma developing in her daughter. We conducted whole-exome sequencing on constitutional DNA from the mother and her daughter and identified a previously unreported nonsense mutation (c.3533G>A; p.Trp1178*) in the chromatin remodelling gene, SMARCA4, that was present in both individuals and was subject to nonsense-mediated decay. Tumour analysis by Sanger sequencing revealed a somatic SMARCA4 mutation in both the mother (c.2438+1G>T) and her daughter (c.3229C>T; p.Arg1077*), which are predicted to be truncating. As immature teratomas are classified as germ cell Tumours, we performed a comprehensive mutation survey of 106 apparently sporadic germ cell Tumours, but did not find any other clearly deleterious SMARCA4 mutations. Recently, inactivating mutations in SMARCA4 have been found in two cases of Rhabdoid Tumour predisposition syndrome type 2. In the light of these findings, renewed efforts to locate previously unobtainable Tumour samples were successfully undertaken. Histopathological and immunohistochemical re-analysis of the daughter's Tumour revealed that it was indeed a Rhabdoid Tumour (atypical teratoid/Rhabdoid Tumour). In this context, the original pathology report of the mother's ovarian Tumour was re-interpreted as describing a Malignant Rhabdoid Tumour of the ovary. This report raises the question as to whether molecular genetic analysis should be included in Tumour classification, alongside more traditional microscopy-based methods. The use of new sequencing technologies, particularly when applied to archived samples, will lead to many more 'molecular rediagnoses'. This is the earliest known case of Rhabdoid Tumour predisposition syndrome type 2 and the first described case with an autosomal dominant pattern of inheritance, only discovered through an exome sequencing project. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.