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Chromothripsis-mediated small cell lung carcinoma.
Rekhtman, Natasha; Tischfield, Sam E; Febres-Aldana, Christopher A; Lee, Jake June-Koo; Chang, Jason C; Herzberg, Benjamin O; Selenica, Pier; Woo, Hyung Jun; Vanderbilt, Chad M; Yang, Soo-Ryum; Xu, Fei; Bowman, Anita S; da Silva, Edaise M; Noronha, Anne Marie; Mandelker, Diana L; Mehine, Miika; Mukherjee, Semanti; Blanco-Heredia, Juan; Orgera, John J; Nanjangud, Gouri J; Baine, Marina K; Aly, Rania G; Sauter, Jennifer L; Travis, William D; Savari, Omid; Moreira, Andre L; Falcon, Christina J; Bodd, Francis M; Wilson, Christina E; Sienty, Jacklynn V; Manoj, Parvathy; Sridhar, Harsha; Wang, Lu; Choudhury, Noura J; Offin, Michael; Yu, Helena A; Quintanal-Villalonga, Alvaro; Berger, Michael F; Ladanyi, Marc; Donoghue, Mark T A; Reis-Filho, Jorge S; Rudin, Charles M.
Afiliación
  • Rekhtman N; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Tischfield SE; Memorial Sloan Kettering Cancer Center, New York, New York, United States.
  • Febres-Aldana CA; Memorial Sloan Kettering Cancer Center, New York, United States.
  • Lee JJ; Memorial Sloan Kettering Cancer Center, New York, United States.
  • Chang JC; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Herzberg BO; Columbia University Medical Center, United States.
  • Selenica P; Memorial Sloan Kettering Cancer Center, New York, United States.
  • Woo HJ; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Vanderbilt CM; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Yang SR; Memorial Sloan Kettering Cancer Center, New York, New York, United States.
  • Xu F; Memorial Sloan Kettering Cancer Center, United States.
  • Bowman AS; Memorial Sloan Kettering Cancer Center, New York, United States.
  • da Silva EM; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Noronha AM; Memorial Sloan Kettering Cancer Center, United States.
  • Mandelker DL; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Mehine M; Memorial Sloan Kettering Cancer Center, New York, United States.
  • Mukherjee S; Memorial Sloan Kettering Cancer Center, New York, United States.
  • Blanco-Heredia J; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Orgera JJ; Memorial Sloan Kettering Cancer Center, United States.
  • Nanjangud GJ; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Baine MK; Memorial Sloan Kettering Cancer Center, New York, New York, United States.
  • Aly RG; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Sauter JL; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Travis WD; Memorial Sloan Kettering Cancer Center, New York, United States.
  • Savari O; University Hospitals of Cleveland, Cleveland, Ohio, United States.
  • Moreira AL; New York University, New York, New York, United States.
  • Falcon CJ; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Bodd FM; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Wilson CE; Memorial Sloan Kettering Cancer Center, United States.
  • Sienty JV; New York University, New York, NY, United States.
  • Manoj P; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Sridhar H; Memorial Sloan Kettering Cancer Center, United States.
  • Wang L; St. Jude Children's Research Hospital, Memphis, United States.
  • Choudhury NJ; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Offin M; Memorial Sloan Kettering Cancer Center, Hillsdale, NJ, United States.
  • Yu HA; Memorial Sloan Kettering Cancer Center, New York, United States.
  • Quintanal-Villalonga A; Memorial Sloan Kettering Cancer Center, New York, New York, United States.
  • Berger MF; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Ladanyi M; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Donoghue MTA; Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Reis-Filho JS; AstraZeneca (United States), United States.
  • Rudin CM; Memorial Sloan Kettering Cancer Center, New York, New York, United States.
Cancer Discov ; 2024 Aug 26.
Article en En | MEDLINE | ID: mdl-39185963
ABSTRACT
Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that is typically associated with tobacco exposure and inactivation of RB1 and TP53 genes. Here we performed detailed clinicopathologic, genomic and transcriptomic profiling of an atypical subset of SCLC that lacked RB1 and TP53 co-inactivation and arose in never/light smokers. We found that most cases were associated with chromothripsis - massive, localized chromosome shattering - recurrently involving chromosomes 11 or 12, and resulting in extrachromosomal (ecDNA) amplification of CCND1 or co-amplification of CCND2/CDK4/MDM2, respectively. Uniquely, these clinically aggressive tumors exhibited genomic and pathologic links to pulmonary carcinoids, suggesting a previously uncharacterized mode of SCLC pathogenesis via transformation from lower-grade neuroendocrine tumors or their progenitors. Conversely, SCLC in never-smokers harboring inactivated RB1 and TP53 exhibited hallmarks of adenocarcinoma-to-SCLC derivation, supporting two distinct pathways of plasticity-mediated pathogenesis of SCLC in never-smokers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancer Discov Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancer Discov Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos