TY - JOUR

T1 - Somatic evolution of marine transmissible leukemias in the common cockle, Cerastoderma edule

AU - Bruzos, Alicia

AU - Santamarina, Martin

AU - Garcia-Souto, Daniel

AU - Diaz, Seila

AU - Rocha, Sara

AU - Zamora, Jorge

AU - Lee, Yunah

AU - Viña-Feás, Alejandro

AU - Quail, Michael A.

AU - Otero, Iago

AU - Pequeño-Valtierra, Ana

AU - Temes, Javier

AU - Rodriguez-Castro, Jorge

AU - Aramburu, Leyre

AU - Vidal-Capón, André

AU - Villanueva, Antonio

AU - Costas, Damián

AU - Rodríguez, Rosana

AU - Prieto, Tamara

AU - Tomás, Laura

AU - Alvariño, Pilar

AU - Alonso, Juana

AU - Cao, Asunción

AU - Iglesias, David

AU - Carballal, María J.

AU - Amaral, Ana M.

AU - Balseiro, Pablo

AU - Calado, Ricardo

AU - El Khalfi, Bouchra

AU - Izagirre, Urtzi

AU - de Montaudouin, Xavier

AU - Pade, Nicolas G.

AU - Probert, Ian

AU - Ricardo, Fernando

AU - Ruiz, Pamela

AU - Сказина, Мария Александровна

AU - Smolarz, Katarzyna

AU - Pasantes, Juan J.

AU - Villalba, Antonio

AU - Ning, Zemin

AU - Seok Ju, Young

AU - Posada, David

AU - Demeulemeester, Jonas

AU - Baez-Ortega, Adrian

AU - Tubio, Jose M. C.

PY - 2023/10/2

Y1 - 2023/10/2

N2 - Transmissible cancers are malignant cell lineages that spread clonally between individuals. Several such cancers, termed bivalve transmissible neoplasia (BTN), induce leukemia-like disease in marine bivalves. This is the case of BTN lineages affecting the common cockle, Cerastoderma edule, which inhabits the Atlantic coasts of Europe and northwest Africa. To investigate the evolution of cockle BTN, we collected 6,854 cockles, diagnosed 390 BTN tumors, generated a reference genome and assessed genomic variation across 61 tumors. Our analyses confirmed the existence of two BTN lineages with hemocytic origins. Mitochondrial variation revealed mitochondrial capture and host co-infection events. Mutational analyses identified lineage-specific signatures, one of which likely reflects DNA alkylation. Cytogenetic and copy number analyses uncovered pervasive genomic instability, with whole-genome duplication, oncogene amplification and alkylation-repair suppression as likely drivers. Satellite DNA distributions suggested ancient clonal origins. Our study illuminates long-term cancer evolution under the sea and reveals tolerance of extreme instability in neoplastic genomes.

AB - Transmissible cancers are malignant cell lineages that spread clonally between individuals. Several such cancers, termed bivalve transmissible neoplasia (BTN), induce leukemia-like disease in marine bivalves. This is the case of BTN lineages affecting the common cockle, Cerastoderma edule, which inhabits the Atlantic coasts of Europe and northwest Africa. To investigate the evolution of cockle BTN, we collected 6,854 cockles, diagnosed 390 BTN tumors, generated a reference genome and assessed genomic variation across 61 tumors. Our analyses confirmed the existence of two BTN lineages with hemocytic origins. Mitochondrial variation revealed mitochondrial capture and host co-infection events. Mutational analyses identified lineage-specific signatures, one of which likely reflects DNA alkylation. Cytogenetic and copy number analyses uncovered pervasive genomic instability, with whole-genome duplication, oncogene amplification and alkylation-repair suppression as likely drivers. Satellite DNA distributions suggested ancient clonal origins. Our study illuminates long-term cancer evolution under the sea and reveals tolerance of extreme instability in neoplastic genomes.

UR - https://www.mendeley.com/catalogue/b90b0dbc-1621-3f79-983c-17a180cb4664/

U2 - 10.1038/s43018-023-00641-9

DO - 10.1038/s43018-023-00641-9

M3 - Article

JO - Nature Cancer

JF - Nature Cancer

SN - 2662-1347

ER -