Clinical Cancer Genomics Program

遗传咨询培训计划（GCTP）由一名全职博士遗传咨询师（GC）组成，他也在NIH生物伦理学部门任职。临床癌症遗传学服务的部分人员包括1名兼职和2名全职临床癌症遗传学主任，以及1名由接触者转为临床癌症遗传学主任的全职病人护理协调员。CCR今年资助了第三名全职GC，我们最后的候选人将作为合同工被引入，直到她可以转换为直接聘用GS的挑战。我们的遗传学家职位仍然开放，并继续在美国医学遗传学和基因组学学院和CCR职业页面上刊登广告。Chimene Kesserwan博士通过她的NIH研究合作者职位为临床、研究和T/N WES种系和体细胞变异策展提供支持。Sheila Rajagopal医生可以处理紧急的临床问题，并参加我们每周的病例会议，讨论复杂的患者，审查检测决定，结果解释。CCGP已取得以下成就：1)遗传咨询师培训计划（GCTP）：与国家人类基因组研究所（NHGRI）就NIH GCTP达成谅解备忘录，有效期至2025年3月31日。今年的学生津贴增加了15%，必须支付本财政年度我们6名学生的费用，估计为16,853美元。这是一个永久性的增长，会影响谅解备忘录年度预算谅解备忘录，因此AO正在处理修改预算的文书工作。NCI资助的GCTP助理主任积极参加每周的行政会议和执行委员会的任务。今年，她与一位外部顾问一起参加了课程评估。她参与了GCTP申请人的面试和排名。她是学生指导不可或缺的一部分，包括独立和共同指导学生论文。她是癌症标准化患者轮转和开发的唯一讲师，并教授癌症基因组学高级主题课程。贾马尔博士于2023年因三门课程的工作而获得约翰霍普金斯大学彭博公共卫生学院的卓越教学奖。在2023年8月，Jamal博士将完成宾夕法尼亚大学高等教育工作者的正义、公平、多样性和包容性证书课程，目的是影响GCTP学生的种族多样性。她为重新认证计划做出了贡献。Meltzer和Calzone提交了一封支持信。CCGS GCs接受学生的临床经验和指导。为学生提供癌症基因研究机会的摘要，以考虑他们的研究论文和CCGS的委员会服务。贾马尔博士继续在美国国立卫生研究院临床中心生物伦理学部门工作50%。这种关系有利于CCR，通过真实的伦理案例加强GC教育，促进CCR伦理咨询。2)临床癌症遗传学服务（CCGS）： CCGS为研究人员提供方案制定方面的支持；管理基因偶然发现；根据临床或方案要求提供遗传咨询和检测；并进行种系和/或体细胞变异解释。CCGS仍未被临床中心认可为正式的咨询服务。我们继续保持一个中央电子邮件和电话热线咨询请求。从2022年7月10日至2023年7月10日，CCGS的新咨询人数从216人增加到286人。有65个要求审查图表和/或基因检测报告。由于时间限制，只有1个GC跟踪该活动，图表审查减少了。大多数CCGS测试是由外部实验室进行的。我们与两个实验室签订了合同，正在建立第三个实验室。gc完成测试请求表格，PCC输入POTS信息，并在实验室发票到来时核对以验证测试和收费。CAN 8036225支付所有测试费用，以避免影响实验室合同的付款拖欠。AO每季度与PI CAN核对一次。今年，CCGS与CCR合作概述了这一进程，并评估了建立中央支付机制的必要性。最后的决定是维持现有的过程，并开发一个SOP来涵盖这些过程，并简化AO工作量以协调测试费用。无法付款的私人机构将使用外部医疗服务机制。Gulley博士开始探索病理学实验室（LP）的选择，以扩大他们的测试平台，包括CLIA批准的生殖细胞测试。aldap博士获得了CCGS 2022-23种系测试量/类型，以告知这项工作。CCGS转变为一种基于提供者/患者偏好的亲自就诊和远程医疗的混合医疗服务模式。GCs作为团队的一部分被嵌入到6项服务中：肾脏、血液恶性肿瘤、间皮瘤；前列腺癌;肺;和遗传性胃癌。DCRI开发了一个患者在线门户网站家族史问卷，该问卷预先填充了CRIS谱系。DCRI向CCGS展示了这个工具，允许我们测试并提供反馈，在2023年7月26日，开发人员演示了最终产品，现在转移到测试环境中。这可能会在未来几个月内部署在CRIS，这可能会增加CCGS的病人能力。肿瘤/正常全外显子组测序（T/N WES） CCGS为LP T/N WES检测提供临床支持。CCGS的作用包括：测试前遗传教育和咨询；医疗和家族史收集；同意;种系变异策展，在每周LP外显子组签注上展示变异证据，并公布结果。从2022年7月10日至2023年7月10日，有182个T/N WES转介，高于2022年的49个。CCGS PCC是所有NIH的T/N WES同意请求的中心联系人，包括NIAID GC （N=14转诊）和儿科和神经肿瘤学病例（N=76转诊）。对于不在临床中心的T/N WES病例，唾液或口腔拭子试剂盒将邮寄给患者，并附有预付的联邦快递退货标签。CCGS购买套件并支付邮寄费用。去年报告中提到的CCR淋巴瘤组的T/N WES增加了。CCGS支持学生教育，包括GCTP学生的临床经验和研究论文。今年，我们为遗传学机会、学习、发展、赋权和网络（GOLDEN）项目的两名博士后提供的概念获得了批准。批准了一个新的后备员额，第二个副员额由现有的CCGS CAN提供。我们确定了几个有兴趣从事遗传咨询职业的GOLDEN学生，他们没有被GCTP接受。很多人都不是本地人，但有一个正在申请，另一个正在考虑这个选择。3)基因组变异管理和临床管理：解释基因组变异是一个挑战。ClinGen建立了一个中心资源来定义基因组变异的临床相关性，并召集了几个工作组、工作组、基因管理专家小组和变异管理专家小组（VCEP）。Grace Fasaye继续担任CDH1 VCEP的成员。Alex Lebensohn是美国临床肿瘤学会恶性胸膜间皮瘤治疗指南的专家小组成员。她还参加了FDA倡导小组/间皮瘤聆听会议。所有团队成员都参与常规临床工作，以验证发现具有不确定意义的变异的患者的变异分类，特别是如果患者自检测以来已经过了相当长的时间。Yi Liu领导NIH T/N WES项目的生殖系变异策展，Calzone博士对所有变异分类和报告内容的准确性进行质量审查。卡尔宗尼博士负责阿波罗博士方案奥拉帕尼方案NCT04858334的体细胞变异管理。Chimene Kesserwan博士提供了这些变异解释的确认，直到找到替代的遗传学家。

The Genetic Counseling Training Program (GCTP) is staffed by one full-time PhD genetic counselor (GC) who also holds an appointment in the NIH Department of Bioethics. The Clinical Cancer Genetics Service (CCGS) is partially staffed with 1 part-time and 2 full-time clinical GCs and 1 full-time patient care coordinator (PCC) converted from a contactor to a GS position this year. CCR funded a 3rd full-time GC this year and our final candidate is being brought in as a contractor until she can be converted to a GS position given challenges as a direct GS hire. Our geneticist position remains open and continues to be advertised with the American College of Medical Genetics and Genomics and on the CCR Careers page. Dr. Chimene Kesserwan provides support for clinical, research, and T/N WES germline and somatic variant curation through her NIH Research Collaborator position. Dr. Sheila Rajagopal is available for urgent clinical issues and attends our weekly case conference to discuss complex patients, review testing decisions, result interpretations. The CCGP has achieved the following: 1) Genetic Counselor Training Program (GCTP): The MOU with the National Human Genome Research Institute (NHGRI) for the NIH GCTP in place through March 31, 2025. This year student stipends had a 15% increase and must cover the cost for our 6 students estimated at $16,853 for this fiscal year. This is a permanent increase that impacts the MOU annual budget MOU so the AO iworking on paperwork to amend the budget. NCI funded GCTP Assistant Director actively participates in weekly administrative meetings and Executive Committee tasks. This year she participated in a curriculum review with an outside consultant. She is involved in interviewing and ranking GCTP applicants. She is integral in student advising including independent and co-advising student thesis. She was the sole instructor for the Cancer Standardized Patient Rotation and developed, and taught the Advanced Topics in Cancer Genomics course. Dr. Jamal received the Johns Hopkins Bloomberg School of Public Health for Excellence in Teaching in 2023 associated with her work on three courses. In 8/2023, Dr. Jamal will complete a certificate program in Justice, Equity, Diversity, and Inclusion for Higher Educators at the UPenn with the aim of influencing the racial diversity of GCTP students. She contributed to the reaccreditation package and Drs. Meltzer and Calzone submitted a letter of support. CCGS GCs accept students for clinical experiences and mentoring. Students are provided a summary of cancer genetic research opportunities to consider for their Research Thesis and CCGS serves on committees as indicated. Dr. Jamal continues 50% effort in the NIH Clinical Center Department of Bioethics. This relationship benefits CCR by enhancing GC education with real ethical cases and facilitating CCR ethics consults. 2) Clinical Cancer Genetics Service (CCGS): CCGS provides investigator support in protocol development; manage genetic incidental findings; provide genetic counseling and testing as clinically or protocol indicated; and perform germline and/or somatic variant interpretation. CCGS continues not to be recognized by the Clinical Center as a formal consult service. We continue to maintain a central email and phone line for consult requests. From 7/10/2022-7/10/2023 CCGS saw 286 new consults up from 216. There were 65 requests for chart and/or genetic test report reviews. Chart reviews decreased as only 1 GC tracked this activity given time constraints. Most CCGS tests are conducted by outside laboratories. We have contracts with 2 laboratories and are establishing a 3rd. GCs complete the test request forms, PCC enters POTS information and reconciles when the laboratory invoice comes in to validate the test and charge. CAN 8036225 pays for all tests to avoid payment delinquency which affects laboratory contracts. Quarterly the AO reconciles with the PI CAN.This year CCGS worked with CCR to outline the process and assess need for a central payment mechanism. The final decison was to maintain the existing process and develop a SOP to cover the procedures and streamline the AO workload to reconcile test charges. PIs unable to pay will use the Outside Medical Services mechanism. Dr. Gulley began exploring options with Laboratory of Pathology (LP) to expand their testing platform to include CLIA approved germline testing. Dr. Aldape was provided with CCGS 2022-23 germline test volume/type to inform this effort. CCGS transitioned to a hybrid care delivery model seeing patients in person and telemedicine based on provider/patient preference. GCs are embedded as part of the team in 6 services: Kidney, Hematologic Malignancies, Mesothelioma; Prostate; Lung; and Inherited Gastric Cancer. DCRI developed a patient online portal family history questionnaire which pre-populates the CRIS Pedigree. DCRI demonstrated the tool to CCGS, allowed us to test and provide feedback, and on 7/26/2023 the developers demo'd the final product which now moves to the test environment. This may be deployed in CRIS within the next few months which could increase CCGS patient capacity. Tumor/Normal Whole Exome Sequencing (T/N WES) CCGS provides clinical support for the LP T/N WES test. CCGS roles involve: pretest genetic education and counseling; medical and family history collection; consent; germline variant curation, presentation of variant evidence at the weekly LP Exome Signout, and result disclosure. From 7/10/2022-7/10/2023 there were 182 T/N WES referrals, up from 49 in 2022. The CCGS PCC is the central contact for T/N WES consent requests for all NIH including NIAID GC (N=14 referrals) and Pediatric and Neuro Oncology Cases (N=76 referrals). For T/N WES cases not at the Clinical Center, saliva or buccal swab kits are mailed to the patient with a pre-paid return Fedex label. CCGS purchases the kits and covers mailing costs. The increase in T/N WES by the CCR Lymphoma team mentioned in last years' report has increased. CCGS supports student education including GCTP students for clinical experiences and research thesis. This year our concept for two post bacs from the Genetics Opportunities, Learning, Development, Empowerment and Networking (GOLDEN) Program was approved. One new post bac was approved with the second Vice slot coming from the existing CCGS CAN. We identified several GOLDEN students interested in pursuing a career in genetic counseling who were not accepted to a GCTP. Many are not local, but one is applying and a 2nd is considering the option. 3) Genomic Variant Curation and Clinical 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, Task Forces, Gene Curation Expert Panels, and Variant Curation Expert Panels (VCEP). Grace Fasaye continues as a member on the CDH1 VCEP. Alex Lebensohn serves on the Expert Panel for the American Society of Clinical Oncology's Treatment of Malignant Pleural Mesothelioma Guidelines. She also participated in the FDA Advocacy Panel/Mesothelioma Listening Session. All team members participate in routine clinical work of 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. Dr. Chimene Kesserwan provides the confirmation of these variant interpretations until a replacement geneticist is hired.