PT  - JOURNAL ARTICLE
AU  - Snehal B Patel
AU  - Colin McCormack
AU  - Jennelle C Hodge
TI  - Non-fusion mutations in endometrial stromal sarcomas: what is the potential impact on tumourigenesis through cell cycle dysregulation?
AID  - 10.1136/jclinpath-2020-206432
DP  - 2020 Dec 01
TA  - Journal of Clinical Pathology
PG  - 830--835
VI  - 73
IP  - 12
4099  - http://jcp.bmj.com/content/73/12/830.short
4100  - http://jcp.bmj.com/content/73/12/830.full
SO  - J Clin Pathol2020 Dec 01; 73
AB  - Targeted next-generation sequencing using the 50-gene Ion AmpliSeq Cancer Hotspot Panel v2 identified two significant point mutations in endometrial stromal sarcomas (ESS). Case 1 is a uterine mass from a quadragenarian woman with a karyotype lacking any known ESS rearrangements but demonstrated to have a CTNNB1-activating mutation (c.133T>C, p.[Ser45Pro]). Analysis of a uterine mass from case 2, a sexagenarian woman, revealed biallelic CDKN2A-inactivating mutations (c.172C>T, p.[Arg58Ter] and a deletion). Break-apart studies to identify YWHAE, JAZF1 and PHF1 rearrangements were negative in both tumours. We propose a model in which these point mutations may affect cell proliferation, converging at Wnt signalling and G1-S checkpoint control, that independently or in concert with a rare gene fusion result in ESS tumour development or progression.