222
Sequencing to Discover Biomarkers to Personalize
Cancer Treatment
A sequencing-based method for personalized analysis of rearranged ends (PARE)
in individual tumors identifi es biomarkers that could subsequently be used to
track cancer using patient blood samples. The concept of the utilization of rear-
ranged ends for development of personalized biomarkers has attracted much
attention owing to its clinical applicability. Although targeted next-generation
sequencing (NGS) for recurrent rearrangements has been successful in hemato-
logic malignancies, its application to solid tumors is problematic due to the pau-
city of recurrent translocations. However, copy-number breakpoints (CNBs),
which are abundant in solid tumors, can be utilized for identifi cation of rearranged
ends. The approach relies on massively parallel sequencing by the use of SOLiD
platform (Life Technologies) to fi nd translocations and rearrangements in solid
tumors. After fi nding such rearrangements in breast and colorectal cancer (CRC)
samples, further studies have used PARE to track cancer treatment response,
recurrence, and metastasis in CRC patients. Targeted NGS at copy-number break-
points (TNGS-CNB) has been used in CRC (Kim et al. 2014a ). For deduction of
CNBs, a novel competitive SNP (cSNP) microarray method was developed entail-
ing CNB-region refi nement by competitor DNA. Results indicate that TNGS-
CNB, with its utility for identifi cation of rearrangements in solid tumors, can be
successfully applied in the clinical laboratory for cancer-relapse and therapy-
response monitoring.
This is an important step in bringing NGS technologies to personalized patient
care. Most tumors do not contain rearrangements, but the location of these rear-
rangements varies from one individual to the other, making them good biomarker
candidates. Previous studies on sequencing individuals’ genomes were focused on
single-letter changes, but later studies looked for the swapping of entire sections of
the tumor genome. Rearrangements were found in CRC genomes. Because most
clinically important tumors contain DNA rearrangements, the PARE approach holds
promise for fi nding patient-specifi c biomarkers that can be used to improve the
treatment of a variety of cancers.
The cost of PARE was reportedly around $5,000 per assay, though the cost is
expected to go down as sequencing prices drop and read quality and length
improve. As PARE becomes affordable, it will be a helpful addition for physi-
cians to tailor patient care and may become a useful supplement to traditional
monitoring by imaging or other approaches. The method holds potential for mon-
itoring cancer and guiding treatment, e.g. it may help differentiate between indi-
viduals whose cancers are cured by surgery alone and those who require follow-up
with aggressive chemotherapy or radiation following surgery. PARE will be avail-
able for many cancer patients within 2–3 years, depending largely on sequencing
costs.
10 Personalized Therapy of Cancer