Molecular Analysis of High-grade Serous Ovarian Carcinoma with and Without Associated Serous Tubal Intra-epithelial Carcinoma

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Oct 19

PMID 29042553

Citations 108

Authors

Jennifer Ducie

Fanny Dao

Michael Considine

Narciso Olvera

Patricia A Shaw

Robert J Kurman

Ie-Ming Shih

Robert A Soslow

Leslie Cope

Douglas A Levine

Affiliations

Soon will be listed here.

Abstract

Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~ 50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. The RNA sequence and the miRNA data did not identify any clear separation between cases with and without STIC lesions. HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases.High-grade serous carcinomas (HGSCs) are associated with precursor lesions (STICs) in the fallopian epithelium in only half of the cases. Here the authors report the molecular analysis of HGSCs with and without associated STICs and show similar profiles supporting a common origin for all HGSCs.

Citing Articles

The miRNA and PD-1/PD-L1 signaling axis: an arsenal of immunotherapeutic targets against lung cancer.

Yadav R, Khatkar R, Yap K, Kang C, Lyu J, Singh R Cell Death Discov. 2024; 10(1):414.

PMID: 39343796 PMC: 11439964. DOI: 10.1038/s41420-024-02182-1.

Combined assembloid modeling and 3D whole-organ mapping captures the microanatomy and function of the human fallopian tube.

Crawford A, Forjaz A, Bons J, Bhorkar I, Roy T, Schell D Sci Adv. 2024; 10(39):eadp6285.

PMID: 39331707 PMC: 11430475. DOI: 10.1126/sciadv.adp6285.

Unveiling G-protein coupled receptors as potential targets for ovarian cancer nanomedicines: from RNA sequencing data analysis to in vitro validation.

Khetan R, Eldi P, Lokman N, Ricciardelli C, Oehler M, Blencowe A J Ovarian Res. 2024; 17(1):156.

PMID: 39068454 PMC: 11282829. DOI: 10.1186/s13048-024-01479-0.

Fallopian Tube-Derived High-Grade Serous Cancers Influence Ovarian Production of Norepinephrine and Generate Specific Metabolomic Signatures.

Bergsten T, Lusk H, Haughan M, Guerrero J, Levy S, Lantvit D ACS Pharmacol Transl Sci. 2024; 7(7):2185-2195.

PMID: 39022349 PMC: 11249642. DOI: 10.1021/acsptsci.4c00238.

High-grade serous ovarian cancer (HGSOC) with fallopian tube involvement.

Tanase A, Solomon-Condriuc I, Mogos R, Costachescu G, David C, Buzduga C Rom J Morphol Embryol. 2024; 65(2):325-329.

PMID: 39020548 PMC: 11384032. DOI: 10.47162/RJME.65.2.20.

References

Konecny G, Wang C, Hamidi H, Winterhoff B, Kalli K, Dering J . Prognostic and therapeutic relevance of molecular subtypes in high-grade serous ovarian cancer. J Natl Cancer Inst. 2014; 106(10). PMC: 4271115. DOI: 10.1093/jnci/dju249. View

Kinde I, Bettegowda C, Wang Y, Wu J, Agrawal N, Shih I . Evaluation of DNA from the Papanicolaou test to detect ovarian and endometrial cancers. Sci Transl Med. 2013; 5(167):167ra4. PMC: 3757513. DOI: 10.1126/scitranslmed.3004952. View

Visvanathan K, Vang R, Shaw P, Gross A, Soslow R, Parkash V . Diagnosis of serous tubal intraepithelial carcinoma based on morphologic and immunohistochemical features: a reproducibility study. Am J Surg Pathol. 2011; 35(12):1766-75. PMC: 4612640. DOI: 10.1097/PAS.0b013e31822f58bc. View

Chui M, Wang Y, Wu R, Seidman J, Kurman R, Wang T . Loss of ALDH1A1 expression is an early event in the pathogenesis of ovarian high-grade serous carcinoma. Mod Pathol. 2014; 28(3):437-45. PMC: 4344882. DOI: 10.1038/modpathol.2014.89. View

Eckert M, Pan S, Hernandez K, Loth R, Andrade J, Volchenboum S . Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube. Cancer Discov. 2016; 6(12):1342-1351. PMC: 5164915. DOI: 10.1158/2159-8290.CD-16-0607. View

Verhaak R, Tamayo P, Yang J, Hubbard D, Zhang H, Creighton C . Prognostically relevant gene signatures of high-grade serous ovarian carcinoma. J Clin Invest. 2012; 123(1):517-25. PMC: 3533304. DOI: 10.1172/JCI65833. View

Sherman-Baust C, Kuhn E, Valle B, Shih I, Kurman R, Wang T . A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development. J Pathol. 2014; 233(3):228-37. PMC: 4149901. DOI: 10.1002/path.4353. View

Kurman R, Shih I . Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm. Hum Pathol. 2011; 42(7):918-31. PMC: 3148026. DOI: 10.1016/j.humpath.2011.03.003. View

Kindelberger D, Lee Y, Miron A, Hirsch M, Feltmate C, Medeiros F . Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship. Am J Surg Pathol. 2007; 31(2):161-9. DOI: 10.1097/01.pas.0000213335.40358.47. View

10.

Sutherland K, Berns A . Cell of origin of lung cancer. Mol Oncol. 2010; 4(5):397-403. PMC: 5527931. DOI: 10.1016/j.molonc.2010.05.002. View

11.

Waggott D, Chu K, Yin S, Wouters B, Liu F, Boutros P . NanoStringNorm: an extensible R package for the pre-processing of NanoString mRNA and miRNA data. Bioinformatics. 2012; 28(11):1546-8. PMC: 3356845. DOI: 10.1093/bioinformatics/bts188. View

12.

Law C, Chen Y, Shi W, Smyth G . voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 2014; 15(2):R29. PMC: 4053721. DOI: 10.1186/gb-2014-15-2-r29. View

13.

Levine E, Blazer 3rd D, Kim M, Shen P, Stewart 4th J, Guy C . Gene expression profiling of peritoneal metastases from appendiceal and colon cancer demonstrates unique biologic signatures and predicts patient outcomes. J Am Coll Surg. 2012; 214(4):599-606. PMC: 3768122. DOI: 10.1016/j.jamcollsurg.2011.12.028. View

14.

Semenova E, Nagel R, Berns A . Origins, genetic landscape, and emerging therapies of small cell lung cancer. Genes Dev. 2015; 29(14):1447-62. PMC: 4526731. DOI: 10.1101/gad.263145.115. View

15.

Dobin A, Davis C, Schlesinger F, Drenkow J, Zaleski C, Jha S . STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2012; 29(1):15-21. PMC: 3530905. DOI: 10.1093/bioinformatics/bts635. View

16.

Dressman H, Berchuck A, Chan G, Zhai J, Bild A, Sayer R . An integrated genomic-based approach to individualized treatment of patients with advanced-stage ovarian cancer. J Clin Oncol. 2007; 25(5):517-25. DOI: 10.1200/JCO.2006.06.3743. View

17.

Kim J, Coffey D, Ma L, Matzuk M . The ovary is an alternative site of origin for high-grade serous ovarian cancer in mice. Endocrinology. 2015; 156(6):1975-81. PMC: 5393339. DOI: 10.1210/en.2014-1977. View

18.

Bonome T, Levine D, Shih J, Randonovich M, Pise-Masison C, Bogomolniy F . A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer. Cancer Res. 2008; 68(13):5478-86. PMC: 7039050. DOI: 10.1158/0008-5472.CAN-07-6595. View

19.

Gross A, Kurman R, Vang R, Shih I, Visvanathan K . Precursor lesions of high-grade serous ovarian carcinoma: morphological and molecular characteristics. J Oncol. 2010; 2010:126295. PMC: 2860809. DOI: 10.1155/2010/126295. View

20.

Kuhn E, Wang T, Doberstein K, Bahadirli-Talbott A, Ayhan A, Sehdev A . CCNE1 amplification and centrosome number abnormality in serous tubal intraepithelial carcinoma: further evidence supporting its role as a precursor of ovarian high-grade serous carcinoma. Mod Pathol. 2016; 29(10):1254-61. PMC: 6557162. DOI: 10.1038/modpathol.2016.101. View