Today in
@science.org:
We are pleased to present our last work entitled:
"Concurrent L1 retrotransposition events promote reciprocal translocations in human tumorigenesis"
by Zumalave et al.
www.science.org/doi/10.1126/...
Gracias a las más de 100 personas que asististeis esta mañana al CiMUS para la conversación divulgativa sobre la historia detrás del descubrimiento de nuestra reciente publicación en Science. Ver a gente sentada en el suelo y de pie para escucharnos fue simplemente alucinante. GRACIAS!!!! 🙌
Key findings:
1️⃣ L1s drive large-scale rearrangements including translocations (not just insertions)
2️⃣ Frequency of these events was largely underestimated by short-reads
3️⃣ They occur EARLY, thus potentially acting as drivers
#Genomics #CancerResearch #MobileDNA @nanoporetech.com
Huge congrats to Sonia Zumalave @bernardo-rodriguez.bsky.social @mobilegenomes.bsky.social es.bsky.social Jose Tubio & team!
Happy to have (modestly) contributed!
@inserm.fr @insermpacacorse.bsky.social
@cnrsbiologie.bsky.social @univcotedazur.bsky.social @ircan.bsky.social
Of note, this work completes a trilogy of seminal papers in the field of cancer retrotransposition from our group over the past few years (Tubio et al. PMID 32024998; Rodriguez-Martin et al. PMID 25082706).
Our results highlight L1 activity as a more significant player in tumour genome plasticity than previously anticipated using short-read sequencing.
This suggests that somatic retrotransposition activation is not merely a consequence of the genomic chaos typical of later stages of tumour progression. Instead, it appears to be an early mutational process, highly active and a major cause of genome instability in some tumours.
5. We developed timing approaches to analyse retrotransposon insertions and found that ~65% of the insertions are occur early before the first whole-genome doubling event, including L1-mediated reciprocal translocations and other retrotransposon-mediated structural variations.
4. Our analysis found that the highest burden of L1-mediated rearrangements coincided with biallelic mutations in Fanconi anemia (FA) genes. This observation provides a compelling clinical correlate to recent experimental studies.
Additionally, synchronicity of distinct L1 insertion events also promotes reciprocal inversions and complex structural variants. This synchronised interaction between two L1 molecules has not been previously reported, although recently confirmed in vitro by Kathy Burns lab.
Our results demonstrate that reciprocal translocations can arise from either one or two independent retrotransposition events, with the latter being more frequent.
3. Our analysis of the L1 bridges mediating reciprocal translocations revealed events where the cDNA from two independent, but synchronous, L1 somatic insertions "recombined", leading to exchanges between non-homologous chromosomes.
Using an independent tumor cohort spanning low to high L1 activity, we estimate that retrotransposon-mediated rearrangements arise at a frequency of one event per 60 somatic retrotranspositions.
2. Rearrangements mediated by retrotransposon insertions are more frequent and variable than previously reported. Notably, L1 insertion is identified as a primary mechanism driving reciprocal translocations.
1. Long-read sequencing analysis uncovers a hidden landscape of cryptic somatic retrotransposition events and internal structures: We found that up to 43% of insertions identified using long-read sequencing are missed by short-read sequencing analysis.
Through the development of novel algorithms, we have uncovered new types of retrotransposon-mediated rearrangements occurring in vivo in cancer, and characterised the dynamics of somatic retrotransposition during tumour evolution with unprecedented resolution.
Our key findings:
Here, we conducted long-read single-molecule sequencing on a carefully selected cohort of 10 human tumours exhibiting exceptionally high rates of somatic retrotransposition, encompassing over 6,000 events.
Today in
@science.org:
We are pleased to present our last work entitled:
"Concurrent L1 retrotransposition events promote reciprocal translocations in human tumorigenesis"
by Zumalave et al.
www.science.org/doi/10.1126/...
✨ Guest lectures are an important part of how we foster scientific exchange at St. Anna CCRI. This week we had the pleasure of hosting Jose Tubio (CiMUS, Spain), who spoke on the impact of mobile DNA in human cancer and disease.
@mobilegenomes.bsky.social
@cimususc.bsky.social
Congratulations to Paula Otero
@PaulaOteroSchez, a very talented PhD student in our group, who has just successfully defended her thesis on somatic mutation of hepatitis B infected liver tissues. Se becomes the seventh star shining in our team’s academic galaxy!
Paula Otero PhD dissertation this Monday at CIMUS
Upcoming #CiMUSseminar on Monday ⤵️
🗣 Dr. @timcoorens.bsky.social from @ebi.embl.org :
🧪 "Somatic mutations across normal tissues: past, present, future"
📅 June 30, 1 PM
📍 Theatre room, CiMUS
#RedeCiGUS #FondosEuropeos
@mobilegenomes.bsky.social @usc.gal
Congratulations to Ana Oitaben, a brilliant PhD student from our group, who has just successfully defended her thesis. Her dedication and talent have earned her a well-deserved doctorate — and she becomes the sixth star shining in our team’s academic galaxy!
We had a great time in Barcelona in the 45th Frontier Scientists Workshop. Interesting topics and discussion on Genomics and Evolution. Thank you Korean Academy of Science and Technology (KAST) for organizing this together with Centre for Genomic Regulation (CRG)
Hello World!
