Junne Kamihara, MD
Junne Kamihara, MD
Dana-Farber Cancer Institute
Determining the Prevalence of Germline Cancer Predisposition Mutations Among a Highrisk Cohort of Pediatric Oncology Patients
Grant Term: July 1, 2014 – June 30, 2015
The overall goal of my research is to understand inherited genetic factors that lead to the initiation or promotion of childhood cancers. This project aims to determine the prevalence of germline mutations found among a cohort of pediatric oncology patients with a suspected cancer predisposition. This study will compare the frequency of mutations found using a custom next generation sequencing panel vs. standard testing that relies on an iterative candidate gene approach. A subset of patients in whom no mutation is found using either approach will be studied using a comprehensive whole exome sequencing analysis of parent-child trios.
Since the time of the original proposal, we have finalized the protocol, patient, family member, and genetic counselor consent forms, and developed a genetic counselor survey and patient family and medical history questionnaire for inclusion in the study. We piloted this questionnaire among a group of families considered to be at high risk for cancer predisposition and created a linked database for genotype/phenotype data before revising it for study inclusion. We have also since launched the multidisciplinary Pediatric Cancer Risk Program (PCRP) clinic where I have been seeing patients twice a month. Through mutation testing and subsequent screening we have already detected two malignancies in asymptomatic family members. One of these masses was detected early enough to prevent progression to worsening or metastatic disease, validating the significant impact that finding disease-causing mutations can have for patients. This clinic provides the ideal infrastructure for this study and through this clinic we have identified the first cohort of families to be enrolled.
The protocol, consents, and appendices have undergone significant reviews and revisions. These were submitted to the DFCI IRB and this process has been a productive experience. A significant note put forward by the IRB, for example, was the potential ethical dilemma of including siblings in the whole exome sequencing part of the study. This raised the issue of balancing the scientific merit of sequencing siblings with the ethical challenges of potentially discovering incidental genetic risk mutations in an otherwise healthy minor. The last few months have been productive in developing the infrastructure for this project and we are now well equipped to attain target accrual for achieving my research aims.
January 23, 2017 Update
Dr. Junne Kamihara is an attending physician in pediatric oncology at the Dana-Farber Cancer Institute and Boston Children's Hospital and Instructor of Pediatrics at Harvard Medical School. She graduated from Harvard College with a degree in biochemistry, after which she spent one year as a Rockefeller fellow teaching primary school in Kenya. After volunteering in a health clinic in a Nairobi slum during this time, her decision to become a physician was solidified. Dr. Kamihara returned to Boston where she completed her M.D. at Harvard Medical School and a Ph.D. in Human Genetics from MIT. She then completed her pediatric residency training at Boston Children's Hospital, followed by a fellowship in pediatric hematology/oncology at the Dana-Farber Cancer Institute (DFCI) and Boston Children's Hospital during which time she also served as chief fellow.
Dr. Kamihara has a passion for understanding what underlies the development of cancer in children, with a particular focus on the genetic drivers of pediatric cancers. She is co-director of the Pediatric Cancer Genetic Risk Program at DFCI, a program which she helped to establish. The Cancer Genetic Risk Program is a multidisciplinary program that serves families who face the possibility that information contained in their genes could put their children at increased risk for developing cancer or a secondary malignancy. In the era of advanced genomic technologies, this program not only seeks to provide comprehensive care for these families but also to include the latest research and cutting edge technologies to help develop better diagnostics and risk-minimizing cancer surveillance. Dr. Kamihara's complementary research program focuses on understanding the genetic causes of hereditary cancers. Ongoing studies led by Dr. Kamihara includes a study of high-risk pediatric patients using whole exome sequencing platforms to identify known or novel predisposition genes, and a study aimed at determining the prevalence of inherited mutations among individuals with childhood thyroid neoplasms.
Many parents ask, "Why did my child develop cancer?" The goal of this project is to identify mutations in cancer risk genes and address how often some children develop cancer due to an inherited genetic risk. Children who are considered to be at high risk of carrying an inherited predisposition to cancer have been invited to enroll on this study. Participants include individuals with multiple cancers, children who have strong family history of cancers, or who children who develop a tumor at an unexpectedly young age. Dr. Kamihara and her team are using whole exome sequencing to determine how frequently inherited mutations occur, comparing this to conventional genetic testing. Family and medical histories are incorporated into the analyses. Parents have also been invited to participate to enable further sequencing analysis when applicable. Genetic results which are curated by an expert panel are then returned to the patient and family via a genetic counselor with expertise in counseling patients about genetic risk. Further analysis of the germline sequence is also performed to facilitate broader gene discovery. Funding from the Conquer Cancer Foundation/Strike 3 Foundation Young Investigator Award provided the support needed to launch this pediatric cancer genetics research platform at its most critical time.
This project began from an initial limited gene panel test to become a whole exome sequencing study for all participants, due to the rapid advancement and availability of sequencing technologies and analytical strategies. Dr. Kamihara and her team have implemented this sequencing pipeline and have fine-tuned the logistics of obtaining genomic DNA from patients on study. This has allowed them to create a robust infrastructure to support broader studies to address the prevalence of hereditary risk among unselected groups of pediatric cancer patients. Such studies are key to helping understand the inherited genetic risks that lead to childhood cancers.
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