Clinical Cancer Genomics Program

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Project Summary: The Genetic Counseling Training Program (GCTP) is staffed by one full-time PhD level genetic counselor (GC) who also holds an appointment in the NIH Department of Bioethics. CCGS is currently partially staffed with 1 full-time PhD GC who just joined the team, 1 part-time and 3 full-time clinical cancer GCs and 1 full-time patient care coordinator. The clinical cancer geneticist position remains open. The CCGP has achieved the following: 1) GCTP: The MOU with the National Human Genome Research Institute (NHGRI) for the NIH Genetic Counseling Training Program (GCTP) in place through the program conclusion in 2027. This MOU is the last and the budget reflects an annual cost reduction as student cohorts complete the program. Dr. Jamal, the NCI training director, participates in the weekly administrative meetings, and Executive Committee tasks. She continues to be the instructor and preceptor for the Cancer Standardized Patient Rotation, advises independently and co-advises student thesis. She has a 50% effort in GCTP and 50% effort in the NIH Department of Bioethics and became a bioethics attending this year. This benefits CCR enabling Dr. Jamal to enhance her genetic counseling education with real life ethical case studies while facilitating CCR ethics consults. CCGS GCs accept students for clinical experiences for in-person and telemedicine encounters. Students are provided a summary of cancer genetic research opportunities to consider for their Research Thesis and are available to serve on committees as indicated. 2) CCGS: Consults: CCGS provides investigator protocol development support; Incidental findings clinical services; provides genetic counseling and testing as indicated; and germline and/or somatic variant interpretation. CCGS continues not to be recognized by the Clinical Center as a formal consult service. Our submission was approved but the Clinical Center they have not createed CRIS consult orders. We maintain a central email and phone line for consult requests with team specific checklists. We maintain our liaison with NHGRI so cancer consults submitted in error are referred back to us. From 7/10/2024-7/10/2025 CCGS had 268 new genetic counseling/testing consults, down (N=23) from 2023-2024 (not including Tumor/Normal Whole Exome Sequencing [T/N WES]). This does not include data of direct referrals reeived by Michaela Verna as she is on maternity leave. Additionally, these data do not include volume for Dr. Raygada who transferred to the CCGP from the Pediatric and Neuro Oncology Branches. The CCGS PCC handles all genetic test POTS for Dr. Raygada who just joined CCGS. From 7/10/2024-7/10/2025 Dr. Raygada ordered 36 tests. Most germline tests ordered by CCGS are conducted by outside laboratories with pricing agreements. This year we established a PO for one lab and began work to establish a contract as instructed. Purchasing transferred us 7/2025 to the clinical arm which instead recommended large blanket POTS, implemented 7/18/2025. Test request forms for outside labs are completed by the genetic counselor that saw the patient. The CCGS PCC enters POTS information and reconciles all tests when the laboratory invoice is received. CAN 8036225 pays all laboratory tests to avoid payment delinquency. Quarterly the AO reconciles with the PI CAN. CCGS maintains a hybrid care delivery model seeing patients in person and via telemedicine. CCGS retrieves blood, saliva, or buccal swabs from phlebotomy or the clinic for laboratory shipment. Most germline samples are collected using saliva or buccal swab kits sent to the patient by the lab, mailed back to the lab, and tracked by the PCC. GCs are embedded in 5 services based on consult numbers and/or protocols requiring germline testing: Kidney, Hematology, Mesothelioma; Prostate; and Pediatrics (Dr. Raygada transition). Hematology patients are the most complex taking more time than other diseases including whether a variant somatic or germline if cultured fibroblasts were not tested, and complex donor testing psychosocial issues. The Gastric team diminished with the departure of Dr. Davis but the GC continues to field questions from patients needing providers to assume their care. DCRI has not launched the online patient portal for the family history questionnaire. Questionnaires are submitted securely to the CCGP PCC and entered manually. 3) Tumor/Normal Whole Exome Sequencing (T/N WES): CCGS provides clinical support for the Laboratory of Pathologies (LP) T/N WES test including: pretest genetic education and counseling; medical and family history collection; patient consent; specimen collection either in person or kits mailed; pedigree collection and CRIS entry; and germline result disclosure. Somatic results are delivered by the oncologist. The CCGS PCC schedules all T/N WES patients including other institute referrals. 7/10/2024-7/10/2025 there were 74 T/N WES referrals, down from 192 in 2024. One factor is test cost with non-CCR investigators needing to cover the cost. Volume may increase when the Synthesis protocol IRB001891 opens. The CCGS PCC is the NIH central contact for T/N WES consent requests including NIAID (N=5 ) and Margarita Raygada (N=5) who has joined CCGS. For T/N WES remote encounters, saliva or buccal swab kits are mailed with pre-paid return Fedex label. CCGS purchases the kits, covers mailing costs tracks kits. Calzone and Liu participate in weekly LP Exome Signout providing germline variant reviews, the evidence, initial classification, draft the variant interpretation report section, and present cases to Molecular Pathologist(s). Cases where the T/N WES encounter is remote, saliva or buccal swab kits are mailed with a pre-paid return Fedex label. CCGS purchases the kits and covers mailing costs. The PCC tracks each kit. 4) GC Education: CCGS supports education and mentoring of students interested in a GC career or are pursuing GC training. This included a post bac whose first application to a training program was unsuccessful. She shadowed cases and worked on a systematic review with Dr. Jamal and was accepted into a fall 2025 program. We also support GCTP students for clinical experiences and research thesis. This year we also supported a Baylor College of Medicine GC summer student doing her 6 week summer rotation and a second summer student from the NIH GCTP. NHGRI transitioned the Global Genetics and Genomics Community (G3C) education website onto genome.gov. The plan to update all existing cases based on current evidence was halted given budget and staffing issues. No new cases are being created. 3) Genomic Variant Curation and Management: Interpreting genomic variants is a challenge. ClinGen built a central resource to define the clinical relevance of genomic variants and convened several Working Groups (WG), Task Forces (TF), Gene Curation Expert Panels, and Variant Curation Expert Panels (VCEP) which CCGS actively participates. The CCGS representation on these panels is limited. Grace Fasaye continues as a member of the Gastric Cancer (formally CDH1) VCEP. All team members participate in verifying variant classifications from patients found to harbor a variant of uncertain significance, especially if a considerable length of time has passed since the patient was tested. Yi Liu leads the germline variant curation for the NIH T/N WES program with Dr. Calzone performing the quality review of all variant classifications and accuracy of report content. Dr. Calzone leads the somatic variant curation for Dr. Apolo's protocol Olaparib protocol NCT04858334 and our former geneticist, Dr. Chimene Kesserwan, provides confirmation of those initial variant interpretations. Alex Lebensohn was an invited participant on the Expert Panel for the American Society of Clinical Oncology's Treatment of Malignant Pleural Mesothelioma Guidelines PMID: 39778125.