SWI/SNF-deficient undifferentiated malignancies: Where to draw the line Editorial
| Authors: | Tessier-Cloutier, B.; Kleinman, C. L.; Foulkes, W. D. |
| Title: | SWI/SNF-deficient undifferentiated malignancies: Where to draw the line |
| Abstract: | Alterations in chromatin remodelling genes are increasingly recognised as drivers of undifferentiated malignancies. In atypical teratoid/rhabdoid tumours (ATRTs) and extracranial rhabdoid tumours (ECRTs), inactivation of SMARCB1 underlies >95% of cases. In the remainder, the culprit is another SWI/SNF family member, SMARCA4. By contrast, in small cell carcinoma of the ovary hypercalcaemic type (SCCOHT), SMARCA4 deficiency is by far the most common driver mechanism, while SMARCB1 alterations are rarely seen. It is unclear why alterations are so heavily weighted towards one or another subunit based on site alone, but both have become essential markers for the diagnosis and management of these undifferentiated lesions. Core SMARCA4-deficient undifferentiated malignancies share an aggressive clinical course and show an overlapping morphologic phenotype. In their study, Andrianteranagna, Cyrta and colleagues used DNA methylation and gene expression profiling to compare two subsets of SMARCA4-deficient malignancies diagnosed as SCCOHT and ECRT. Their work gives further insight into the subtle molecular spectrum of SMARCA4-deficient tumours, and their distinction from ATRT and ECRT with SMARCB1 inactivation. The characterisation of these molecular features is likely to play an important role in the future as we try to establish a clinically meaningful framework for the diagnosis and management of these lesions. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| Keywords: | unclassified drug; gene mutation; note; endometrium carcinoma; gene expression; gene expression profiling; sonic hedgehog protein; embryo development; dna methylation; genomic instability; myc protein; carcinoma; ovary carcinoma; gene inactivation; gene silencing; monophenol monooxygenase; mediastinum tumor; oxidative phosphorylation; uterus sarcoma; anaplastic carcinoma; cyclin dependent kinase 4; chromatin assembly and disassembly; rhabdoid tumor; hox protein; enhancer region; cyclin dependent kinase 6; protein serine threonine kinase inhibitor; nucleic acid binding protein; germline mutation; brm protein; brg1 protein; epigenome; immune checkpoint inhibitor; undifferentiated endometrial carcinoma; dedifferentiated carcinoma; human; small cell carcinoma of the ovary hypercalcemic type; atypical teratoid rhabdoid tumor; malignant neoplasm; swi/snf related matrix associated actin dependent regulator of chromatin subfamily b member 1; protein swi/snf related matrix associated actin dependent regulator of chromatin subfamily c member 1; protein swi/snf related matrix associated actin dependent regulator of chromatin subfamily e member 1; extracranial rhabdoid tumor; hlf cell line (lung fibroblast); mle-12 cell line; smarca4 deficient uterine sarcoma; switch sucrose non fermentable deficient undifferentiated malignancy; thoracic smarca4 deficient undifferentiated tumor |
| Journal Title: | Journal of Pathology |
| Volume: | 256 |
| Issue: | 2 |
| ISSN: | 0022-3417 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2022-02-01 |
| Start Page: | 139 |
| End Page: | 142 |
| Language: | English |
| DOI: | 10.1002/path.5836 |
| PUBMED: | 34767264 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Note -- Export Date: 1 February 2022 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work