☆ 4.7 Article

New insights in sarcoma oncogenesis: a comprehensive analysis of a large series of 160 soft tissue sarcomas with complex genomics

JOURNAL OF PATHOLOGY (2011)

Journal

JOURNAL OF PATHOLOGY

Volume 223, Issue 1, Pages 64-71

Publisher

WILEY-BLACKWELL

DOI: 10.1002/path.2787

Keywords

undifferentiated sarcoma; leiomyosarcoma; CGH; transcriptome; PTEN; DKK1; RB1

Funding

INSERM
Institut Curie
INCa [PL007]
PHRC [2007/05]
Conticanet Network
Fondation de France
Paris Descartes University
Assistance Publique-Hopitaux de Paris
Ligue Nationale Contre le Cancer

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Abstract

Adult soft tissue sarcomas (STS) are rare tumours of mesenchymal lineage. Based on cytogenetic and comparative genomic hybridization (CGH) data, they can be divided into 'STS with simple genomics', displaying a characteristic genetic alteration, and 'STS with complex genomics' (SCG), where multiple genomic alterations occur. This latter group is mostly composed of leiomyosarcomas (LMS) and pleiomorphic undifferentiated tumours previously labelled as 'malignant fibrous histiocytomas' (MFH), corresponding in fact to myxofibrosarcomas (MFS), pleiomorphic liposarcomas/rhabdomyosarcomas (P-LPS, P-RMS), and undifferentiated pleiomorphic sarcomas (UPS). Their pathobiology is still not well understood, leading to challenges in diagnosis and therapeutic management. We report here a comprehensive study encompassing array-CGH and transcriptome analysis data of a large series of 160 SCG. Non-supervised clustering of transcriptome data led to the identification of five groups of tumours, one of them (group A) corresponding to well-differentiated LMS and the other four (B-E) to 'MFH' and poorly differentiated LMS. Welch analysis of transcriptome data in these groups allowed us to retrieve several genes of potential interest. Among them, RB1 alteration is a constant thread in SCG, often associated with RBL2 loss. PTEN tumour suppressor deletion would also stand out as a major recurrent event, especially in groups A, C, and D. The WNT canonical pathway could be potentially involved, as demonstrated by up-regulation of one of its inhibitors, DKK1, in groups D and E, whereas DKK1 is significantly down-regulated in groups A, B, and C. These data suggest a very complex interplay between pathways downstream of PTEN and the WNT canonical pathway, providing new hints about SCG pathobiology and their potential therapeutic targets. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Retrospective analysis of adjuvant treatment for localized, operable uterine leiomyosarcoma

Jomjit Chantharasamee, Karlton Wong, Pasathorn Potivongsajarn, Amir Qorbani, Neda Motamed, Sandra Brackert, Joshua Cohen, Bartosz Chmielowski, Anusha Kalbasi, Jianyu Rao, Scott Nelson, Arun Singh

Summary: There is currently no standard adjuvant treatment protocol for localized uterine leiomyosarcoma (uLMS). This study aims to determine the benefit of adjuvant chemotherapy for uLMS. The results showed that patients who received any form of adjuvant therapy had a slightly longer disease-free survival, but the difference was not significant. Tumor size and mitotic rate were identified as independent prognostic factors for worse outcomes. Therefore, the need for adjuvant therapy for resected uLMS remains in question.

CANCER MEDICINE (2022)