Yes / Background: Soft tissue sarcomas are heterogeneous and a major complication in their management is that the existing
classification scheme is not definitive and is still evolving. Leiomyosarcomas, a major histologic category of soft tissue sarcomas,
are malignant tumours displaying smooth muscle differentiation. Although defined as a single group, they exhibit a wide range of
clinical behaviour. We aimed to carry out molecular classification to identify new molecular subgroups with clinical relevance.
Methods: We used gene expression profiling on 20 extra-uterine leiomyosarcomas and cross-study analyses for molecular
classification of leiomyosarcomas. Clinical significance of the subgroupings was investigated.
Results: We have identified two distinct molecular subgroups of leiomyosarcomas. One group was characterised by high
expression of 26 genes that included many genes from the sub-classification gene cluster proposed by Nielsen et al. These
sub-classification genes include genes that have importance structurally, as well as in cell signalling. Notably, we found a
statistically significant association of the subgroupings with tumour grade. Further refinement led to a group of 15 genes that
could recapitulate the tumour subgroupings in our data set and in a second independent sarcoma set. Remarkably, cross-study
analyses suggested that these molecular subgroups could be found in four independent data sets, providing strong support for
their existence.
Conclusions: Our study strongly supported the existence of distinct leiomyosarcoma molecular subgroups, which have clinical
association with tumour grade. Our findings will aid in advancing the classification of leiomyosarcomas and lead to more
individualised and better management of the disease. / Alexander Boag Sarcoma Fund.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/14821 |
| Date | 09 August 2016 |
| Creators | Lee, Stephanie, Roe, T., Mangham, D.C., Fisher, C., Grimer, R.J., Judson, I. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Published version |
| Rights | © 2016 Cancer Research UK. All rights reserved. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/, CC-BY |
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