title: Next-generation sequencing: a powerful tool for the discovery of molecular markers in breast ductal carcinoma in situ.
abstract: Mammographic screening leads to frequent biopsies and concomitant overdiagnosis of breast cancer, particularly ductal carcinoma in situ (DCIS). Some DCIS lesions rapidly progress to invasive carcinoma, whereas others remain indolent. Because we cannot yet predict which lesions will not progress, all DCIS is regarded as malignant, and many women are overtreated. Thus, there is a pressing need for a panel of molecular markers in addition to the current clinical and pathological factors to provide prognostic information. Genomic technologies such as microarrays have made major contributions to defining subtypes of breast cancer. Next-generation sequencing (NGS) modalities offer unprecedented depth of expression analysis through revealing transcriptional boundaries, mutations, rare transcripts and alternative splice variants. NGS approaches are just beginning to be applied to DCIS. Here, the authors review the applications and challenges of NGS in discovering novel potential therapeutic targets and candidate biomarkers in the premalignant progression of breast cancer.
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Hitchintan
authors.initials: H
authors.lastname: Kaur
authors.forename: Shihong
authors.initials: S
authors.lastname: Mao
authors.forename: Seema
authors.initials: S
authors.lastname: Shah
authors.forename: David H
authors.initials: DH
authors.lastname: Gorski
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Krawetz
authors.forename: Bonnie F
authors.initials: BF
authors.lastname: Sloane
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Mattingly
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis*; D002278:Carcinoma in Situ / Q000175:diagnosis*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis*; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA
chemical_list: D014408:Biomarkers, Tumor