Chapters:
3:00 What is the current landscape in cancer susceptibility testing?
6:00 The challenge of the next decade: improving test interpretation
8:15 Beyond DNA: the launch of the first commercially available paired DNA/RNA sequencing.
9:00: According to Ambry’s own data, RNA testing has had an impact similar to the introduction of del/dup analysis in 2006.
11:58: The question arises yet again: what are our responsibilities with regard to re-contact? The need for re-contact is “something we should expect and it should be part of our conversations with patients” but – Holly adds – decisions about re-contact are something “each clinic has to make on their own regarding their bandwidth”
16:40 Ambry’s test looks at variations in the splicing profile that can tell us what a variant does at the RNA level.
19:00 Despite success in identifying pathogenic variants and clarifying VUS’s, splice sight testing is the “tip of the iceberg.” Is there more to come? Other potential targets for RNA testing include allele specific expression and differences in expression levels …
22:00 Chicken & Egg: we benefit the most from RNA testing of the genes we understand the best, but… RNA testing is also a way to understand more about the splicing landscape of the genes we know the least. For now, because the test is clinical and not research, RNA testing is restricted to 18 of the most well characterized genes on the cancer panel.
25:00 Retrospective studies beginning in 2016 showed that RNA testing could cut down on VUS’s but getting the second test ordered proved to be a significant obstacle. Of 1000 eligible patients offered free RNA sequencing as a follow up to a VUS, they received a second sample from only 1 on 10. “A significant portion of individuals who would have benefitted from this didn’t”
32:40 The next big thing in RNA? Rachid predicts that it will be the ability to detect when a gene is turned on or turned off.
Laura starts out the decade chatting with genetic counselor Holly LaDuca and Rachid Karam, Director of Ambry Translational Genomics Lab, about Ambry’s paired DNA/RNA cancer susceptibility test, which was introduced in 2019. What can RNA testing do to improve detection and interpretation of variants today? And where will it take us next?
