Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a germline CHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic invasive ductal breast carcinoma

Cold Spring Harbor Molecular Case Studies
My Linh ThibodeauSteven J M Jones

Abstract

We describe a woman with the known pathogenic germline variant CHEK2:c.1100delC and synchronous diagnoses of both pelvic genital type leiomyosarcoma (LMS) and metastatic invasive ductal breast carcinoma. CHEK2 (checkpoint kinase 2) is a tumor-suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved in double-strand DNA break repair and cell cycle arrest. The CHEK2:c.1100delC variant is a moderate penetrance allele resulting in an approximately twofold increase in breast cancer risk. Whole-genome and whole-transcriptome sequencing were performed on the leiomyosarcoma and matched blood-derived DNA. Despite the presence of several genomic hits within the double-strand DNA damage pathway (CHEK2 germline variant and multiple RAD51B somatic structural variants), tumor profiling did not show an obvious DNA repair deficiency signature. However, even though the LMS displayed clear malignant features, its genomic profiling revealed several characteristics classically associated with leiomyomas including a translocation, t(12;14), with one breakpoint disrupting RAD51B and the other breakpoint upstream of HMGA2 with very high expression of HMGA2 and PLAG1 This is the first report of LMS genomic profiling in a patient wit...Continue Reading

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Citations

Jul 13, 2018·The American Journal of Surgical Pathology·Jennifer A BennettEsther Oliva
Jun 7, 2018·NPJ Precision Oncology·My Linh ThibodeauSteven J M Jones
Jun 21, 2019·Laboratory Medicine·Narges AnsariHadi Rezaeean

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Datasets Mentioned

BETA
E-MTAB-513
EGAD00001002891
SCV000574565

Methods Mentioned

BETA
hysterectomy
biopsy
biopsies
dissection
RNA-seq

Clinical Trials Mentioned

NCT02155621

Software Mentioned

Body Map
SomaticSignatures
varFilter
ABySS
Trans
Illumina Human Body Map
SAMtools
ArrayExpress
align
CNAseq

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