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Elucidating the pathogenesis of synchronous and metachronous tumors in a woman with endometrioid carcinomas using a whole-exome sequencing approach
- Source :
- Cold Spring Harbor Molecular Case Studies
- Publication Year :
- 2016
-
Abstract
- Synchronous endometrial and ovarian (SEO) carcinomas involve endometrioid neoplasms in both the ovary and uterus at the time of diagnosis. Patients were traditionally classified as having independent primary SEO lesions or as having metastatic endometrioid carcinoma. Recent studies have supported that SEO tumors result from the dissemination of cells from one organ site to another. However, whether this can be considered a “metastasis” or “dissemination” remains unclear. In this report, we performed whole-exome sequencing of tumor samples from a woman with well-differentiated endometrioid SEO tumors and a clinical “recurrent” poorly differentiated peritoneal tumor that was diagnosed 8 years after the complete resection of the SEO tumors. Somatic mutation analysis identified 132, 171, and 1214 nonsynonymous mutations in the endometrial, ovarian, and peritoneal carcinomas, respectively. A unique mutation signature associated with mismatch repair deficiency was observed in all three tumors. The SEO carcinomas shared 57 nonsynonymous mutations, whereas the clinically suspected recurrent carcinoma shared only eight nonsynonymous mutations with the SEO tumors. One of the eight shared somatic mutations involved PTEN; these shared mutations represent the earliest genetic alteration in the ancestor cell clone. Based on analysis of the phylogenetic tree, we predicted that the so-called recurrent peritoneal tumor was derived from the same endometrial ancestor clone as the SEO tumors, and that this clone migrated and established benign peritoneal endometriosis where the peritoneal tumor later arose. This case highlights the usefulness of next-generation sequencing in defining the etiology and clonal relationships of synchronous and metachronous tumors from patients, thus providing valuable insight to aid in the clinical management of rare or ambiguous tumors.
- Subjects :
- 0301 basic medicine
Nonsynonymous substitution
Research Report
endometriosis
Pathology
medicine.medical_specialty
DNA Mutational Analysis
Clone (cell biology)
Loss of Heterozygosity
Ovary
endometrial carcinoma
Biology
Carcinoma, Ovarian Epithelial
ovarian neoplasm
medicine.disease_cause
Polymorphism, Single Nucleotide
Metastasis
Neoplasms, Multiple Primary
03 medical and health sciences
0302 clinical medicine
Germline mutation
INDEL Mutation
Exome Sequencing
medicine
PTEN
Humans
Neoplasms, Glandular and Epithelial
Exome sequencing
Ovarian Neoplasms
Mutation
PTEN Phosphohydrolase
Neoplasms, Second Primary
General Medicine
Middle Aged
medicine.disease
3. Good health
Clone Cells
Endometrial Neoplasms
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
biology.protein
Female
Neoplasm Recurrence, Local
Subjects
Details
- ISSN :
- 23732873
- Volume :
- 3
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cold Spring Harbor molecular case studies
- Accession number :
- edsair.doi.dedup.....f14b1f2e7ed5ce4490d32492df6a7b9b