title: Evaluation of ultra-deep targeted sequencing for personalized breast cancer care.
abstract: BACKGROUND
  The increasing number of targeted therapies, together with a deeper understanding of cancer genetics and drug response, have prompted major healthcare centers to implement personalized treatment approaches relying on high-throughput tumor DNA sequencing. However, the optimal way to implement this transformative methodology is not yet clear. Current assays may miss important clinical information such as the mutation allelic fraction, the presence of sub-clones or chromosomal rearrangements, or the distinction between inherited variants and somatic mutations. Here, we present the evaluation of ultra-deep targeted sequencing (UDT-Seq) to generate and interpret the molecular profile of 38 breast cancer patients from two academic medical centers.
  
  
  METHODS
  We sequenced 47 genes in matched germline and tumor DNA samples from 38 breast cancer patients. The selected genes, or the pathways they belong to, can be targeted by drugs or are important in familial cancer risk or drug metabolism.
  
  
  RESULTS
  Relying on the added value of sequencing matched tumor and germline DNA and using a dedicated analysis, UDT-Seq has a high sensitivity to identify mutations in tumors with low malignant cell content. Applying UDT-Seq to matched tumor and germline specimens from the 38 patients resulted in a proposal for at least one targeted therapy for 22 patients, the identification of tumor sub-clones in 3 patients, the suggestion of potential adverse drug effects in 3 patients and a recommendation for genetic counseling for 2 patients.
  
  
  CONCLUSIONS
  Overall our study highlights the additional benefits of a sequencing strategy, which includes germline DNA and is optimized for heterogeneous tumor tissues.
authors: Olivier
authors: O
authors: Harismendy
authors: Richard B
authors: RB
authors: Schwab
authors: Hakan
authors: H
authors: Alakus
authors: Shawn E
authors: SE
authors: Yost
authors: Hiroko
authors: H
authors: Matsui
authors: Farnaz
authors: F
authors: Hasteh
authors: Anne M
authors: AM
authors: Wallace
authors: Hannah L
authors: HL
authors: Park
authors: Lisa
authors: L
authors: Madlensky
authors: Barbara
authors: B
authors: Parker
authors: Philip M
authors: PM
authors: Carpenter
authors: Kristen
authors: K
authors: Jepsen
authors: Hoda
authors: H
authors: Anton-Culver
authors: Kelly A
authors: KA
authors: Frazer
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D009154:Mutation; D057285:Precision Medicine / Q000379:methods*
chemical_list: D004273:DNA, Neoplasm