Establishing a Framework for the Clinical Translation of Germline Findings in Precision Oncology.
Katherine DixonSean YoungYaoqing ShenMy Linh ThibodeauAlexandra FokErin PleasanceEric ZhaoMartin JonesGeraldine AubertLinlea ArmstrongAlice ViraniDeirdre WeymannKaren A GelmonDan RenoufStephen ChiaIan BosdetS Rod RassekhRebecca J DeyellStephen YipAna FisicEmma TitmussShirin AbadiSteven J M JonesSophie SunAly KarsanMarco A MarraJanessa LaskinHoward LimKasmintan A SchraderPublished in: JNCI cancer spectrum (2020)
Inherited genetic variation has important implications for cancer screening, early diagnosis, and disease prognosis. A role for germline variation has also been described in shaping the molecular landscape, immune response, microenvironment, and treatment response of individual tumors. However, there is a lack of consensus on the handling and analysis of germline information that extends beyond known or suspected cancer susceptibility in large-scale cancer genomics initiatives. As part of the Personalized OncoGenomics program in British Columbia, we performed whole-genome and transcriptome sequencing in paired tumor and normal tissues from advanced cancer patients to characterize the molecular tumor landscape and identify putative targets for therapy. Overall, our experience supports a multidisciplinary and integrative approach to germline data management. This includes a need for broader definitions and standardized recommendations regarding primary and secondary germline findings in precision oncology. Here, we propose a framework for identifying, evaluating, and returning germline variants of potential clinical significance that may have indications for health management beyond cancer risk reduction or prevention in patients and their families.
Keyphrases
- dna repair
- papillary thyroid
- single cell
- immune response
- squamous cell
- quality improvement
- palliative care
- public health
- healthcare
- gene expression
- stem cells
- end stage renal disease
- newly diagnosed
- dna damage
- rna seq
- squamous cell carcinoma
- childhood cancer
- young adults
- genome wide
- clinical practice
- climate change
- copy number
- machine learning
- dendritic cells
- peritoneal dialysis
- health information
- oxidative stress
- social media
- bone marrow
- big data
- replacement therapy