Format

Send to

Choose Destination
JAMA Oncol. 2015 Nov;1(8):1128-32. doi: 10.1001/jamaoncol.2015.1618.

Next-Generation Sequencing of Tubal Intraepithelial Carcinomas.

Author information

1
Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor.
2
Department of Pathology, Massachusetts General Hospital, Boston.
3
Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor.
4
Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor4Department of Urology, University of Michigan, Ann Arbor5Comprehensive Cancer Center, University of Michigan, Ann Arbor.
5
Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor5Comprehensive Cancer Center, University of Michigan, Ann Arbor6Department of Internal Medicine, University of Michigan, Ann Arbor.

Abstract

IMPORTANCE:

High-grade serous carcinoma (HGSC) is the most prevalent and lethal form of ovarian cancer. HGSCs frequently arise in the distal fallopian tubes rather than the ovary, developing from small precursor lesions called serous tubal intraepithelial carcinomas (TICs, or more specifically, STICs). While STICs have been reported to harbor TP53 mutations, detailed molecular characterizations of these lesions are lacking.

OBSERVATIONS:

We performed targeted next-generation sequencing (NGS) on formalin-fixed, paraffin-embedded tissue from 4 women, 2 with HGSC and 2 with uterine endometrioid carcinoma (UEC) who were diagnosed as having synchronous STICs. We detected concordant mutations in both HGSCs with synchronous STICs, including TP53 mutations as well as assumed germline BRCA1/2 alterations, confirming a clonal association between these lesions. Next-generation sequencing confirmed the presence of a STIC clonally unrelated to 1 case of UEC, and NGS of the other tubal lesion diagnosed as a STIC unexpectedly supported the lesion as a micrometastasis from the associated UEC.

CONCLUSIONS AND RELEVANCE:

We demonstrate that targeted NGS can identify genetic alterations in minute lesions, such as TICs, and confirm TP53 mutations as early driving events for HGSC. Next-generation sequencing also demonstrated unexpected associations between presumed STICs and synchronous carcinomas, providing evidence that some TICs are actually metastases rather than HGSC precursors.

PMID:
26181193
PMCID:
PMC4935931
DOI:
10.1001/jamaoncol.2015.1618
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center