title: Genomic differences between pure ductal carcinoma in situ and synchronous ductal carcinoma in situ with invasive breast cancer.
abstract: Although ductal carcinoma in situ (DCIS) precedes invasive ductal carcinoma (IDC), the related genomic alterations remain unknown. To identify the genomic landscape of DCIS and better understand the mechanisms behind progression to IDC, we performed whole-exome sequencing and copy number profiling for six cases of pure DCIS and five pairs of synchronous DCIS and IDC. Pure DCIS harbored well-known mutations (e.g., TP53, PIK3CA and AKT1), copy number alterations (CNAs) and chromothripses, but had significantly fewer driver genes and co-occurrence of mutation/CNAs than synchronous DCIS-IDC. We found neither recurrent nor significantly mutated genes with synchronous DCIS-IDC compared to pure DCIS, indicating that there may not be a single determinant for pure DCIS progression to IDC. Of note, synchronous DCIS genomes were closer to IDC than pure DCIS. Among the clinicopathologic parameters, progesterone receptor (PR)-negative status was associated with increased mutations, CNAs, co-occurrence of mutations/CNAs and driver mutations. Our results indicate that although pure DCIS has already acquired some drivers, more changes are needed to progress to IDC. In addition, IDC-associated DCIS is more aggressive than pure DCIS at genomic level and should really be considered IDC. Finally, the data suggest that PR-negativity could be used to predict aggressive breast cancer genotypes.
authors.affiliation: Department of Microbiology, The Catholic University of Korea, Seoul.|Department of Integrated Research Center for Genome Polymorphism, The Catholic University of Korea, Seoul.
authors.forename: Shinn Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Microbiology, The Catholic University of Korea, Seoul.|Department of Integrated Research Center for Genome Polymorphism, The Catholic University of Korea, Seoul.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Department of Pathology, The Catholic University of Korea, Seoul.
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Microbiology, The Catholic University of Korea, Seoul.|Department of Integrated Research Center for Genome Polymorphism, The Catholic University of Korea, Seoul.
authors.forename: In-Pyo
authors.initials: IP
authors.lastname: Baek
authors.affiliation: Department of Hospital Pathology, The Catholic University of Korea, Seoul.
authors.forename: Sung Hak
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul.
authors.forename: Tae-Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Microbiology, The Catholic University of Korea, Seoul.|Department of Integrated Research Center for Genome Polymorphism, The Catholic University of Korea, Seoul.
authors.forename: Yeun-Jun
authors.initials: YJ
authors.lastname: Chung
authors.affiliation: Department of Pathology, The Catholic University of Korea, Seoul.
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000328:Adult; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D023281:Genomics; D006801:Humans; D008875:Middle Aged; D017422:Sequence Analysis, DNA / Q000379:methods*
keywords: breast cancer; copy number alteration; ductal carcinoma in situ; genomic difference; whole exome
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