Data from <i>BRAF</i> and <i>DIS3</i> Mutations Associate with Adverse Outcome in a Long-term Follow-up of Patients with Multiple Myeloma

• DOI: 10.1158/1078-0432.c.6528056.v1
• Publication Date: 2023-04-01T06:24:08Z
• Authors: Eileen M. Boyle; Cody Ashby; Ruslana G. Tytarenko; Shayu Deshpande; Hongwei Wang; Yan Wang; Adam Rosenthal; Jeffrey Sawyer; Erming Tian; Erin Flynt; Antje Hoering; Sarah K. Johnson; Michael W. Ruther...; Christopher P. Wa...; Michael A. Bauer; Charles Dumontet; Thierry Facon; Sharmilan Thanend...; Carolina D. Schinke; Maurizio Zangari; Frits van Rhee; Bart Barlogie; David Cairns; Graham Jackson; Anjan Thakurta; Faith E. Davies; Gareth J. Morgan; Brian A. Walker
• Keywords: V600E

&lt;div&gt;AbstractPurpose:&lt;p&gt;Copy-number changes and translocations have been studied extensively in many datasets with long-term follow-up. The impact of mutations remains debated given the short time to follow-up most datasets.&lt;/p&gt;Experimental Design:&lt;p&gt;We performed targeted panel sequencing covering 125 myeloma-specific genes loci involved 223 newly diagnosed myeloma samples recruited into one total therapy trials.&lt;/p&gt;Results:&lt;p&gt;As expected, commonly mutated were &lt;i&gt;NRAS, KRAS&lt;/i&gt;, &lt;i&gt;BRAF&lt;/i&gt;, making up 44% patients. Double-Hit &lt;i&gt;BRAF&lt;/i&gt; &lt;i&gt;DIS3&lt;/i&gt; had an on outcome alongside classical risk factors context intensive treatment approach. We able identify both V600E non-V600E mutations, 58% which predicted be hypoactive or kinase dead. Interestingly, hypoactive/kinase dead &lt;i&gt;BRAF&lt;/i&gt;-mutated patients showed co-occurring alterations &lt;i&gt;KRAS, NRAS&lt;/i&gt;, activating suggesting that they play a role oncogenesis multiple by facilitating MAPK activation may lead chemoresistance.&lt;/p&gt;Conclusions:&lt;p&gt;Overall, these data highlight importance mutational screening better understand patient-specific mutation-driven approaches.&lt;/p&gt;&lt;/div&gt;