Clinical sequencing defines the genomic landscape of metastatic colorectal cancer Journal Article


Authors: Yaeger, R.; Chatila, W. K.; Lipsyc, M. D.; Hechtman, J. F.; Cercek, A.; Sanchez-Vega, F.; Jayakumaran, G.; Middha, S.; Zehir, A.; Donoghue, M. T. A.; You, D.; Viale, A.; Kemeny, N.; Segal, N. H.; Stadler, Z. K.; Varghese, A. M.; Kundra, R.; Gao, J.; Syed, A.; Hyman, D. M.; Vakiani, E.; Rosen, N.; Taylor, B. S.; Ladanyi, M.; Berger, M. F.; Solit, D. B.; Shia, J.; Saltz, L.; Schultz, N.
Article Title: Clinical sequencing defines the genomic landscape of metastatic colorectal cancer
Abstract: Metastatic colorectal cancers (mCRCs) are clinically heterogeneous, but the genomic basis of this variability remains poorly understood. We performed prospective targeted sequencing of 1,134 CRCs. We identified splice alterations in intronic regions of APC and large in-frame deletions in CTNNB1, increasing oncogenic WNT pathway alterations to 96% of CRCs. Right-sided primary site in microsatellite stable mCRC was associated with shorter survival, older age at diagnosis, increased mutations, and enrichment of oncogenic alterations in KRAS, BRAF, PIK3CA, AKT1, RNF43, and SMAD4 compared with left-sided primaries. Left-sided tumors frequently had no identifiable genetic alteration in mitogenic signaling, but exhibited higher mitogenic ligand expression. Our results suggest different pathways to tumorigenesis in right-and left-sided microsatellite stable CRC that may underlie clinical differences.
Keywords: mutation; microsatellite instability; colon; reveals; domain; inhibition; trials; primary tumor location; braf mutants
Journal Title: Cancer Cell
Volume: 33
Issue: 1
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2018-01-08
Start Page: 125
End Page: 136.e3
Language: English
ACCESSION: WOS:000419465500013
DOI: 10.1016/j.ccell.2017.12.004
PROVIDER: wos
PMCID: PMC5765991
PUBMED: 29316426
Notes: Article -- Source: Wos
Altmetric Score
MSK Authors
  1. Leonard B Saltz
    555 Saltz
  2. Neal Rosen
    351 Rosen
  3. David Solit
    420 Solit
  4. Neil Howard Segal
    94 Segal
  5. Zsofia Kinga Stadler
    139 Stadler
  6. Marc Ladanyi
    848 Ladanyi
  7. Jinru Shia
    445 Shia
  8. Rona Denit Yaeger
    61 Yaeger
  9. David Hyman
    176 Hyman
  10. Agnes Viale
    203 Viale
  11. Ahmet Zehir
    145 Zehir
  12. Michael Forman Berger
    373 Berger
  13. Efsevia Vakiani
    161 Vakiani
  14. Nancy Kemeny
    334 Kemeny
  15. Jianjiong Gao
    62 Gao
  16. Barry Stephen Taylor
    135 Taylor
  17. Nikolaus D Schultz
    193 Schultz
  18. Daoqi You
    20 You
  19. Aijazuddin Syed
    20 Syed
  20. Sumit   Middha
    51 Middha
  21. Marla   Lipsyc
    3 Lipsyc
  22. Ritika   Kundra
    15 Kundra