The Genomic Landscape of Mucinous Breast Cancer

Fresia Pareja; Ju Youn Lee; David N Brown; Salvatore Piscuoglio; Rodrigo Gularte-Mérida; Pier Selenica; Arnaud Da Cruz Paula; Sasi Arunachalam; Rahul Kumar; Felipe C Geyer; Catarina Silveira; Edaise M da Silva; Anqi Li; Caterina Marchiò; Charlotte K Y Ng; Odette Mariani; Laetitia Fuhrmann; Hannah Y Wen; Larry Norton; Anne Vincent-Salomon; Edi Brogi; Jorge S Reis-Filho; Britta Weigelt

doi:10.1093/jnci/djy216

The Genomic Landscape of Mucinous Breast Cancer

J Natl Cancer Inst. 2019 Jul 1;111(7):737-741. doi: 10.1093/jnci/djy216.

Authors

Fresia Pareja¹, Ju Youn Lee¹, David N Brown¹, Salvatore Piscuoglio^{1

2}, Rodrigo Gularte-Mérida¹, Pier Selenica¹, Arnaud Da Cruz Paula¹, Sasi Arunachalam¹, Rahul Kumar¹, Felipe C Geyer¹, Catarina Silveira^{1

3}, Edaise M da Silva¹, Anqi Li¹, Caterina Marchiò⁴, Charlotte K Y Ng^{1

2}, Odette Mariani⁵, Laetitia Fuhrmann⁵, Hannah Y Wen¹, Larry Norton⁶, Anne Vincent-Salomon⁵, Edi Brogi¹, Jorge S Reis-Filho¹, Britta Weigelt¹

Affiliations

¹ Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
² Institute of Pathology, University Hospital Basel, Basel, Switzerland.
³ GenoMed SA, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
⁴ Department of Medical Sciences, FPO-Canndiolo Cancer Institute, University of Turin, Turin, Italy.
⁵ Départment de Médecine Diagnostique et Théranostique, Institute Curie, Paris, France.
⁶ Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Abstract

Mucinous carcinoma of the breast (MCB) is a rare histologic form of estrogen receptor (ER)-positive/HER2-negative breast cancer (BC) characterized by tumor cells floating in lakes of mucin. We assessed the genomic landscape of 32 MCBs by whole-exome sequencing and/or RNA-sequencing. GATA3 (23.8%), KMT2C (19.0%), and MAP3K1 (14.3%) were the most frequently mutated genes in pure MCBs. In addition, two recurrent but not pathognomonic fusion genes, OAZ1-CSNK1G2 and RFC4-LPP, were detected in 3/31 (9.7%) and 2/31 (6.5%) samples, respectively. Compared with ER-positive/HER2-negative common forms of BC, MCBs displayed lower PIK3CA and TP53 mutation rates and fewer concurrent 1q gains and 16q losses. Clonal decomposition analysis of the mucinous and ductal components independently microdissected from five mixed MCBs revealed that they are clonally related and evolve following clonal selection or parallel evolution. Our findings indicate that MCB represents a genetically distinct ER-positive/HER2-negative form of BC.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma, Mucinous / classification
Adenocarcinoma, Mucinous / genetics*
Adenocarcinoma, Mucinous / pathology
Aged
Biomarkers, Tumor / genetics
Breast Neoplasms / classification
Breast Neoplasms / genetics*
Breast Neoplasms / pathology
Class I Phosphatidylinositol 3-Kinases / genetics
Clonal Evolution / genetics*
Cytoskeletal Proteins / genetics
Estrogen Receptor alpha / genetics
Exome Sequencing
Female
Genetic Predisposition to Disease*
Humans
LIM Domain Proteins / genetics
Middle Aged
Mucins / genetics
Mutation / genetics
Oncogene Proteins, Fusion / genetics
Proteins / genetics
Receptor, ErbB-2 / genetics
Replication Protein C / genetics
Tumor Suppressor Protein p53 / genetics

Substances

Biomarkers, Tumor
Cytoskeletal Proteins
Estrogen Receptor alpha
LIM Domain Proteins
LPP protein, human
Mucins
Oncogene Proteins, Fusion
Proteins
RFC4 protein, human
TP53 protein, human
Tumor Suppressor Protein p53
ornithine decarboxylase antizyme
Class I Phosphatidylinositol 3-Kinases
PIK3CA protein, human
ERBB2 protein, human
Receptor, ErbB-2
Replication Protein C

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States