Limitations and pitfalls of using family letters to communicate genetic risk: a qualitative study with patients and healthcare professionals

European genetic testing guidelines recommend that healthcare professionals (HCPs) discuss the familial implications of any test with a patient and offer written material to help them share the information with family members. Giving patients these “family letters” to alert any relatives of their risk has become part of standard practice and has gone relatively unquestioned over the years. Communication with at-risk relatives will become an increasingly pressing issue as mainstream and routine practice incorporates broad genome tests and as the number of findings potentially relevant to relatives increases. This study therefore explores problems around the use of family letters to communicate about genetic risk. We conducted 16 focus groups with 80 HCPs, and 35 interviews with patients, recruited from across the UK. Data were analyzed thematically and we constructed four themes: 1) HCPs writing family letters: how to write them and why?, 2) Patients’ issues with handing out family letters, 3) Dissemination becomes an uncontrolled form of communication, and 4) When the relative has the letter, is the patient’s and HCP’s duty discharged? We conclude by suggesting alternative and supplementary methods of communication, for example through digital tools, and propose that in comparison to communication by family letter, direct contact by HCPs might be a more appropriate and successful option

How communication of genetic information within the family is addressed in genetic counselling: a systematic review of research evidence

Supporting consultands to communicate risk information with their relatives is key to obtaining the full benefits of genetic health care. To understand how health-care professionals address this issue in clinical practice and what interventions are used specifically to assist consultands in their communication of genetic information to appropriate relatives, we conducted a systematic review. Four electronic databases and four subject-specific journals were searched for papers published, in English, between January 1997 and May 2014. Of 2926 papers identified initially, 14 papers met the inclusion criteria for the review and were heterogeneous in design, setting and methods. Thematic data analysis has shown that dissemination of information within families is actively encouraged and supported by professionals. Three overarching themes emerged: (1) direct contact from genetic services: sending letters to relatives of mutation carriers; (2) professionals' encouragement of initially reluctant consultands to share relevant information with at-risk relatives and (3) assisting consultands in communicating genetic information to their at-risk relatives, which included as subthemes (i) psychoeducational guidance and (ii) written information aids. Findings suggest that professionals' practice and interventions are predicated on the need to proactively encourage family communication. We discuss this in the context of what guidance of consultands by professionals might be appropriate, as best practices to facilitate family communication, and of the limits to non-directiveness in genetic counselling

Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns

Central to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at single-cell resolution. Here, we present 3D Live-Seq—a protocol that integrates live-cell imaging of tumor organoid outgrowth and whole-genome sequencing of each imaged cell to reconstruct evolving tumor cell karyotypes across consecutive cell generations. Using patient-derived colorectal cancer organoids and fresh tumor biopsies, we demonstrate that karyotype alterations of varying complexity are prevalent and can arise within a few cell generations. Sub-chromosomal acentric fragments were prone to replication and collective missegregation across consecutive cell divisions. In contrast, gross genome-wide karyotype alterations were generated in a single erroneous cell division, providing support that aneuploid tumor genomes can evolve via punctuated evolution. Mapping the temporal dynamics and patterns of karyotype diversification in cancer enables reconstructions of evolutionary paths to malignant fitness