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Book: Entwicklung molekularer Marker zur präzisen Klassifikation von mesenchymalen Tumoren

Kölsche, Christian

(Forum Moderne Pathologie /Forum Modern Pathology ; 24)

2021

Abstract: Sarkome sind maligne Tumoren des Weichgewebes und des Knochens. In der aktuellen WHO Klassifikation für Tumoren des Weichgewebes und des Knochens werden mehr als 100 verschiedenen Subtypen unterschieden. Häufig lässt sich die Liniendifferenzierung von ... ...

Series title	Forum Moderne Pathologie /Forum Modern Pathology ; 24
Abstract	Sarkome sind maligne Tumoren des Weichgewebes und des Knochens. In der aktuellen WHO Klassifikation für Tumoren des Weichgewebes und des Knochens werden mehr als 100 verschiedenen Subtypen unterschieden. Häufig lässt sich die Liniendifferenzierung von Sarkomen bei zunehmendem Malignitätsgrad und damit einhergehender Entdifferenzierung nicht mehr eindeutig durch konventionelle Methoden wie Histologie oder Immunphänotypisierung nachweisen. Im diagnostischen Alltag des Pathologen können die Diff...
Keywords	Tumor ; Pathologie ; Tumorpathologie
Language	German
Size	98 p.
Edition	1
Publisher	Shaker Verlag
Document type	Book
Note	Hochschulschriften Medizin
Format	148 x 210
ISBN	9783844074307 ; 3844074309
Database	PDA

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Book ; Thesis: Untersuchungen zur nukleären Lokalisation und Funktion des Proteins "Suppressor of cytokine signaling 1"

Kölsche, Christian

2009

Author's details	vorgelegt von Christian Kölsche
Language	German
Size	IX, 105 Bl., Ill., graph. Darst.
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Heidelberg, Univ., Diss., 2011
HBZ-ID	HT016966250
Database	Catalogue ZB MED Medicine, Health

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2011 E 3223	order for loan	Magazin

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Article ; Online: Methylation classifiers: Brain tumors, sarcomas, and what's next.

Koelsche, Christian / von Deimling, Andreas

Genes, chromosomes & cancer

2022 Volume 61, Issue 6, Page(s) 346–355

Abstract: Tumor classification has evolved over the last decades with technical progress contributing much to our current concepts. Among diagnostic hallmarks, novelties were immunostaining, Fluorescence in situ hybridization, Sanger sequencing followed by massive ...

Abstract	Tumor classification has evolved over the last decades with technical progress contributing much to our current concepts. Among diagnostic hallmarks, novelties were immunostaining, Fluorescence in situ hybridization, Sanger sequencing followed by massive parallel DNA sequencing, and recently, epigenetic analyses have entered the stage. Although each of these techniques was revolutionary and, in some way, also disruptive in certain diagnostic fields, it took years to decades for broad implementation into standard pathological-diagnostic algorithms. In contrast, DNA methylation profiling has been accepted in short time as a game changer with lasting impact on brain tumor classification and with potential for classification of other tumor types. This review provides a brief introduction in DNA methylation-based tumor classification. We present why DNA methylation signatures are attractive diagnostic biomarkers, discuss present achievements and future aims and explain the integration of methylation-based classifiers in diagnostic procedure. Finally, we provide an outlook on the challenges and opportunities associated with DNA methylation-based tumor profiling.
MeSH term(s)	Brain Neoplasms/diagnosis ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; DNA Methylation ; Humans ; In Situ Hybridization, Fluorescence ; Sarcoma/genetics ; Soft Tissue Neoplasms/genetics
Language	English
Publishing date	2022-04-14
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1018988-9
ISSN	1098-2264 ; 1045-2257
ISSN (online)	1098-2264
ISSN	1045-2257
DOI	10.1002/gcc.23041
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Book ; Online ; Thesis: Entwicklung molekularer Marker zur präzisen Klassifikation von mesenchymalen Tumoren

Kölsche, Christian [Verfasser]

2021

Author's details	Christian Kölsche
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Shaker
Publishing place	Düren
Document type	Book ; Online ; Thesis
ISBN	978-3-8440-7430-7 ; 3-8440-7430-9
Database	Digital theses on the web

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Article ; Online: DNA methylation profile discriminates sporadic giant cell granulomas of the jaws and cherubism from their giant cell-rich histological mimics.

Guimarães, Letícia Martins / Baumhoer, Daniel / Andrei, Vanghelita / Friedel, Dennis / Koelsche, Christian / Gomez, Ricardo Santiago / von Deimling, Andreas / Gomes, Carolina Cavalieri

The journal of pathology. Clinical research

2023 Volume 9, Issue 6, Page(s) 464–474

Abstract: Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell- ... ...

Abstract	Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell-rich lesions, including non-ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic GCG and cherubism to test whether DNA methylation patterns can help to distinguish them. Additionally, we compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. DNA methylation analysis was performed for central (n = 10) and peripheral (n = 10) GCG, cherubism (n = 6), NOF (n = 10), ABC (n = 16), GCTB (n = 9), and chondroblastoma (n = 10) using the Infinium Human Methylation EPIC Chip. Central and peripheral sporadic GCG and cherubism share a related DNA methylation pattern, with those of peripheral GCG and cherubism appearing slightly distinct, while central GCG shows overlap with both of the former. NOF, ABC, GCTB, and chondroblastoma, on the other hand, have distinct methylation patterns. The global and enhancer-associated CpG DNA methylation values showed a similar distribution pattern among central and peripheral GCG and cherubism, with cherubism showing the lowest and peripheral GCG having the highest median values. By contrast, promoter regions showed a different methylation distribution pattern, with cherubism showing the highest median values. In conclusion, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions. Conversely, it could discriminate sporadic GCG of the jaws from their giant cell-rich mimics (NOF, ABC, GCTB, and chondroblastoma).
MeSH term(s)	Humans ; Cherubism/diagnosis ; Cherubism/genetics ; Cherubism/pathology ; Granuloma, Giant Cell/diagnosis ; Granuloma, Giant Cell/genetics ; Granuloma, Giant Cell/pathology ; Chondroblastoma/diagnosis ; Chondroblastoma/genetics ; Chondroblastoma/pathology ; DNA Methylation ; Giant Cells/pathology ; Giant Cell Tumor of Bone/diagnosis ; Giant Cell Tumor of Bone/genetics ; Giant Cell Tumor of Bone/pathology ; Bone Neoplasms/diagnosis ; Bone Neoplasms/genetics ; Bone Neoplasms/pathology ; Jaw/pathology
Language	English
Publishing date	2023-08-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2814357-7
ISSN	2056-4538 ; 2056-4538
ISSN (online)	2056-4538
ISSN	2056-4538
DOI	10.1002/cjp2.337
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Article ; Online: [No title information]

Trennheuser, Lukas / Kölsche, Christian / Enk, Alexander H / Hassel, Jessica C

Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG

2020 Volume 18, Issue 8, Page(s) 886–888

Title translation	Pleomorphes dermales Sarkom mit zerebralen Metastasen.
Language	German
Publishing date	2020-07-28
Publishing country	Germany
Document type	Letter
ZDB-ID	2093479-8
ISSN	1610-0387 ; 1610-0379
ISSN (online)	1610-0387
ISSN	1610-0379
DOI	10.1111/ddg.14134_g
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Article ; Online: Pleomorphic dermal sarcoma with cerebral metastasis.

Trennheuser, Lukas / Kölsche, Christian / Enk, Alexander H / Hassel, Jessica C

Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG

2020 Volume 18, Issue 8, Page(s) 886–888

MeSH term(s)	Brain Neoplasms ; Humans ; Sarcoma ; Skin Neoplasms
Language	English
Publishing date	2020-06-18
Publishing country	Germany
Document type	Letter
ZDB-ID	2093479-8
ISSN	1610-0387 ; 1610-0379
ISSN (online)	1610-0387
ISSN	1610-0379
DOI	10.1111/ddg.14134
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Article ; Online: Spindle Cell Sarcoma of the Uterine Corpus With Adipose Metaplasia: Expanding the Morphologic Spectrum of Neoplasms With MEIS1-NCOA2 Gene Fusion.

Kommoss, Felix K F / Kölsche, Christian / Mentzel, Thomas / Schmidt, Dietmar / von Deimling, Andreas / McCluggage, W Glenn / Kommoss, Friedrich

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists

2021 Volume 41, Issue 4, Page(s) 417–422

Abstract: We report a spindle cell sarcoma arising in the uterine corpus of a 26-yr-old patient. The patient underwent a simple hysterectomy and the uterine corpus contained a 9 cm tumor showing nodular and "finger-like" myometrial invasion. Histologically, the ... ...

Abstract	We report a spindle cell sarcoma arising in the uterine corpus of a 26-yr-old patient. The patient underwent a simple hysterectomy and the uterine corpus contained a 9 cm tumor showing nodular and "finger-like" myometrial invasion. Histologically, the tumor was composed of a monomorphic population of atypical spindle cells which contained widespread foci of cytologically benign adipocytes. Immunohistochemistry revealed diffuse strong positivity for CD10, CD56, and CD99 and diffuse weak positive staining with ER and WT1 while smooth muscle markers, S100, TLE1, and cyclin D1 were negative. Total RNA sequencing identified an in-frame fusion between exon 6 of MEIS1 and exon 12 of NCOA2. Copy number analysis revealed few aberrations with no deletions or amplifications identified. No adjuvant therapy was given and the patient is disease-free 9 yr after initial diagnosis. This case represents the second report of a uterine sarcoma harboring a MEIS1-NCOA2/1 gene fusion and expands the morphologic spectrum of recently reported spindle cell sarcomas arising in the genitourinary tract harboring MEIS1-NCOA2/1 gene fusions. This is the first reported case of such tumors with an adipocytic component.
MeSH term(s)	Adult ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/genetics ; Female ; Gene Fusion ; Humans ; Immunohistochemistry ; Metaplasia ; Myeloid Ecotropic Viral Integration Site 1 Protein/genetics ; Nuclear Receptor Coactivator 2/genetics ; Sarcoma/genetics ; Sarcoma/pathology ; Soft Tissue Neoplasms/pathology ; Uterine Neoplasms/genetics
Chemical Substances	Biomarkers, Tumor ; Myeloid Ecotropic Viral Integration Site 1 Protein ; NCOA2 protein, human ; Nuclear Receptor Coactivator 2
Language	English
Publishing date	2021-06-23
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	604859-6
ISSN	1538-7151 ; 0277-1691
ISSN (online)	1538-7151
ISSN	0277-1691
DOI	10.1097/PGP.0000000000000803
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Article ; Online: High-Grade Endometrial Stromal Sarcomas With YWHAE::NUTM2 Gene Fusion Exhibit Recurrent CDKN2A Alterations and Absence of p16 Staining is a Poor Prognostic Marker.

Kommoss, Felix K F / Mar, Lisa-Marie / Howitt, Brooke E / Hanley, Krisztina / Turashvilli, Gulisa / Buslei, Rolf / Irving, Julie A / Dickson, Brendan C / Koelsche, Christian / Sinn, Hans-Peter / Schirmacher, Peter / von Deimling, Andreas / Chiang, Sarah / McCluggage, W Glenn / Croce, Sabrina / Stewart, Colin J R / Lee, Cheng-Han

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2023 Volume 36, Issue 3, Page(s) 100044

Abstract: High-grade endometrial stromal sarcomas (HGESSs) are aggressive uterine tumors harboring oncogenic fusion proteins. We performed a molecular study of 36 HGESSs with YWHAE::NUTM2 gene fusion, assessing co-occurring genetic events, and showed that these ... ...

Abstract	High-grade endometrial stromal sarcomas (HGESSs) are aggressive uterine tumors harboring oncogenic fusion proteins. We performed a molecular study of 36 HGESSs with YWHAE::NUTM2 gene fusion, assessing co-occurring genetic events, and showed that these tumors frequently harbor recurrent events involving the CDKN2A locus on chromosome 9p. Using array-based copy number profiling and CDKN2A fluorescence in situ hybridization, we identified homozygous and hemizygous deletions of CDKN2A in 18% and 14% of tumors (n = 22 analyzed), respectively. While all YWHAE-rearranged HGESSs with retained disomy for CDKN2A were immunohistochemically positive for p16INK4 (p16), all tumors with homozygous deletion of CDKN2A showed complete absence of p16 staining. Of the 2 tumors with a hemizygous deletion of CDKN2A, 1 showed diffuse and strong p16 positivity, whereas the other showed complete absence of staining. In the p16-negative case, we did not find intragenic mutations or DNA promoter methylation to explain the p16 protein loss, implicating other mechanisms in the regulation of protein expression. In our cohort, subclonal or complete absence of p16 staining was associated with worse overall survival compared with positive p16 staining (1-year overall survival: 28.6% vs 90.7%, respectively; n = 32; P < .001), with all 7 patients in the p16-negative group having succumbed to their disease within 2 years of diagnosis. Our results suggested CDKN2A alterations as a cooperative driver of tumorigenesis in a subset of HGESSs with the YWHAE::NUTM2 gene fusion and showed p16 to be a potential prognostic marker.
MeSH term(s)	Female ; Humans ; Endometrial Neoplasms/pathology ; Prognosis ; In Situ Hybridization, Fluorescence ; Sarcoma, Endometrial Stromal/genetics ; Sarcoma, Endometrial Stromal/pathology ; Homozygote ; Sequence Deletion ; Sarcoma/genetics ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Gene Fusion ; 14-3-3 Proteins/genetics ; 14-3-3 Proteins/metabolism
Chemical Substances	Cyclin-Dependent Kinase Inhibitor p16 ; YWHAE protein, human ; 14-3-3 Proteins ; CDKN2A protein, human
Language	English
Publishing date	2023-01-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1016/j.modpat.2022.100044
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Article ; Online: Endometrial Stromal Sarcomas With BCOR Internal Tandem Duplication and Variant BCOR/BCORL1 Rearrangements Resemble High-grade Endometrial Stromal Sarcomas With Recurrent CDK4 Pathway Alterations and MDM2 Amplifications.

Kommoss, Felix K F / Chiang, Sarah / Köbel, Martin / Koelsche, Christian / Chang, Kenneth Tou-En / Irving, Julie A / Dickson, Brendan / Thiryayi, Sakinah / Rouzbahman, Marjan / Rasty, Golnar / von Deimling, Andreas / Lee, Cheng-Han / Turashvili, Gulisa

The American journal of surgical pathology

2022 Volume 46, Issue 8, Page(s) 1142–1152

Abstract: The distinction between low-grade and high-grade endometrial stromal sarcomas (LGESS, HGESS) is increasingly defined by genetics. Recently, variant genomic alterations involving BCOR or BCORL1 have been reported in endometrial stromal sarcoma (ESS), ... ...

Abstract	The distinction between low-grade and high-grade endometrial stromal sarcomas (LGESS, HGESS) is increasingly defined by genetics. Recently, variant genomic alterations involving BCOR or BCORL1 have been reported in endometrial stromal sarcoma (ESS), although it remains unclear whether these justify a diagnosis of LGESS or HGESS. In this study, we describe clinicopathologic and molecular features of ESS with such alterations to help clarify their classification in the spectrum of ESS. We collected a cohort of 13 ESS harboring variant alteration involving BCOR (6 with internal tandem duplication, 1 with EP300::BCOR fusion, 1 with BCOR::LPP fusion) and BCORL1 ( 4 with JAZF1::BCORL1 fusion, 1 with EPC1::BCORL1 fusion). The median patient age at primary diagnosis was 51 years (range: 18 to 70 y). Median tumor size at primary diagnosis was 9.3 cm (range: 4.5 to 21 cm), and extrauterine disease spread (stage IIIB-C) was present in 27%. The tumors were composed of round to spindled cells with cellularity and cytologic atypia ranging from mild to marked and a median mitotic count of 18/10 HPFs (range: 2 to 85/10 HPFs). At least focally myopermeative growth was noted in 8/8 assessable cases. Of 12 patients with follow-up data (median: 25 mo), 4 patients died of disease and 3 were alive with recurrent disease. Unsupervised hierarchical clustering of DNA methylation data together with a large cohort of uterine mesenchymal tumors that included YWHAE::NUTM2 and Z C3H7B::BCOR HGESS and molecularly confirmed LGESS revealed a common methylation signature for all ESS with variant BCOR and BCORL1 alterations and HGESS with YWHAE::NUTM2 and ZC3H7B::BCOR gene fusion. Copy number analysis revealed amplifications of CDK4 and MDM2 , as well as homozygous deletions of CDKN2A/B and NF1 in a subset of tumors. Our results indicate that ESS with BCOR internal tandem duplication and variant BCOR and BCORL1 rearrangements clinically and molecularly resemble conventional HGESS.
MeSH term(s)	Cyclin-Dependent Kinase 4 ; Endometrial Neoplasms/genetics ; Endometrial Neoplasms/pathology ; Female ; Gene Fusion ; Humans ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins c-mdm2/genetics ; Repressor Proteins/genetics ; Sarcoma ; Sarcoma, Endometrial Stromal/genetics ; Sarcoma, Endometrial Stromal/pathology ; Soft Tissue Neoplasms ; Uterine Neoplasms/pathology
Chemical Substances	BCOR protein, human ; BCORL1 protein, human ; Proto-Oncogene Proteins ; Repressor Proteins ; MDM2 protein, human (EC 2.3.2.27) ; Proto-Oncogene Proteins c-mdm2 (EC 2.3.2.27) ; CDK4 protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinase 4 (EC 2.7.11.22)
Language	English
Publishing date	2022-05-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752964-8
ISSN	1532-0979 ; 0147-5185
ISSN (online)	1532-0979
ISSN	0147-5185
DOI	10.1097/PAS.0000000000001909
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