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Next-Generation Sequencing for Hereditary Cancers at AMITA Health

Although most breast, ovarian, prostate, and pancreatic cancers arise sporadically, some are caused by hereditary germline mutations1. Likewise, individuals who screen positive for pathogenic variants of certain genes such as BRCA1 and BRCA2 are at a higher risk for developing hereditary cancer syndromes2.

At the AMITA Health Cancer Institute, novel next-generation sequencing (NGS) technologies play a key role in patient care. Using high depth of coverage, high throughput sequencing, cancer care teams can quickly generate patient risk profiles to direct prophylactic surgical and chemotherapeutic treatment plans.

Gene Sequencing Defined and Redefined 

Since the advent of first-generation sequencing technologies, clinicians have utilized genetic testing to determine patient and familial risk of known single gene mutation disorders. However, these technologies have since evolved to allow for the sequencing of multiple DNA fragments in parallel, which greatly increases the size of sequencing targets. Modern NGS platforms allow for greater throughput and depth of coverage than prior iterations so that clinicians can identify altered, inserted, or deleted nucleotides in multiple gene targets spanning as much as the whole genome. These variants can then be used to generate risk profiles, identify drug targets, and inform clinical decision-making3.

Genetic Counseling and Risk Assessment in Pretest Candidates

In recent years, the landscape of genetic counseling has evolved rapidly due to the integration of sequencing technologies into existing risk evaluation tools. In addition to technological improvements, genetic risk evaluation via NGS has become more accessible and affordable. It has thus become a mainstay in the toolkits of many cancer care teams4. According to the National Comprehensive Cancer Network (NCCN) guidelines published in 2015, patients with histories of hereditary cancer are recommended to undergo genetic testing. This includes those with first- or second-degree relatives who have been diagnosed with cancer as well as patients with a history of cancer themselves5.

At the AMITA Health Cancer Institute, the process of genetic testing is facilitated by board-certified genetic counselors trained to determine appropriate testing modalities, generate and review patient risk profiles, and collaborate with other cancer care team members. A thorough evaluation of a patient’s past medical history and family history is used to select genetic testing candidates. From here, a risk assessment model is used to estimate cancer risk upon positive confirmation of a pathogenic variant.

Multigene Panel Testing: Clinical Applications and Use-Cases

Due to the removal of cost and efficiency barriers to multigene panel testing, next-generation sequencing has become a first-line assay for detecting cancer syndromes in all patients who meet the NCCN guidelines3.

Though common pathogenic variants such as BRCA1 and BRCA2 are most often detected in patients with hereditary cancers, between 4 and 7 percent of patient genomes harbor additional variants that may have possible involvement in malignancy2. Likewise, multigene panel testing can generate genetic profiles that include high-, moderate-, and unknown-risk gene variants, which can open new avenues in designing treatment plans for patients with hereditary cancers.

Modern next-generation genetic testing is noninvasive, can be performed quickly, and has a relatively fast turnaround time compared with its predecessors. Genetic counselors and clinicians can use the information from NGS to collaborate and optimize the detection of medically actionable gene targets as well as minimize the incidence of so-called variants of unknown significance4. Testing can also be limited to one gene for families with a known history of a single pathogenic variant. Additionally, patients who had been previously evaluated for hereditary cancer with genetic testing that predates next-generation sequencing can be re-assessed.

Contact the AMITA Health Cancer Institute to refer a patient for the latest in comprehensive genetic screening.


Physician Profile

Robert O. Maganini, MD

Robert O. Maganini, M.D.

General Surgery

AMITA Health Medical Group Breast Surgery Bartlett
1041 W. Stearns Rd.
Bartlett, IL 60103




  1. Zhang S, Royer R, Li S, et al. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol Oncol. 2011;121(2):353-357. doi:10.1016/j.ygyno.2011.01.020
  2. Tung N, Battelli C, Allen B, et al. Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. Cancer. 2015;121(1):25-33. doi:10.1002/cncr.29010
  3. Price KS, Svenson A, King E, Ready K, Lazarin GA. Inherited Cancer in the Age of Next-Generation Sequencing. Biol Res Nurs. 2018;20(2):192-204. doi:10.1177/1099800417750746
  4. Robson ME, Bradbury AR, Arun B, et al. American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility. J Clin Oncol. 2015;33(31):3660-3667. doi:10.1200/JCO.2015.63.0996
  5. Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL; Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015;17(1):70-87. doi:10.1038/gim.2014.147

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