Next Generation DNA Sequencing Promising in Identifying Targets for Personalized Treatments

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CHICAGO―Next generation DNA sequencing (NGS) shows promise in identifying solid tumors harboring “actionable” genetic alterations that can be targeted for personalized therapy, according to findings from a single-institution study presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting. 

“NGS identified genetic alterations in the majority of patients with advanced epithelial cancers, including actionable abnormalities in a large fraction of this heterogeneous population,” reported lead author Patrick McKay Boland, MD, and coauthors from the Fox Chase Cancer Center in Philadelphia, PA. “NGS shows promise in the diagnostic evaluation of advanced malignancies.”

The coauthors analyzed solid tumor samples for 77 adult patients with NGS of 186 genes.

“An actionable genetic alteration was seen in 47 (64%) of 74 patients successfully tested, with 61% of actionable genetic alterations being amplifications and 38% mutations,” the coauthors reported. “Patients had a median of three genetic alterations (range, 0-0).”

“At least one genetic alteration was seen in 71 (96%) patients,” the team reported.

Genetic alterations identified included “mutations in 65 (60%) samples revealing TP53 (32%), KRAS (10%), PIK3CA (8%), and APC (6%), and amplifications in 38 (35%) , which included MYC (18%), MCL1 (14%), CCND1 (12%), and ERBB2 (7%). Copy number loss (4%), fusion (1%), and deletions (2%) were also discovered,” they noted. 

“The use of molecular targeted therapeutic agents may require the application of sophisticated diagnostic technologies for patients' selection,” Dr. Boland noted. “Next generation DNA sequencing has the ability to identify genetic alterations including mutations, copy number alterations, insertions/deletions and rearrangements in tumor specimens.”

He reported that a proportion of patients in the study who were offered therapy based on genetic alterations found on NGS “reaped clinical benefits. However, 29% of patients who were in this group expired prior to initiation of therapy.”

Therefore, “NGS profiling test may be of greater benefit if pursued earlier on during the course of the disease,” Dr. Boland concluded. For example, for patients with advanced solid malignancies, whose diseases are resistant to standard-of-care therapies, NGS may assist in identifying genetic abnormalities that may direct therapy with approved or investigational agents.

Dr. Boland received a 2013 ASCO Merit Award for this abstract.

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