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
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MSK Authors
  1. Leonard B Saltz
    664 Saltz
  2. Neal Rosen
    379 Rosen
  3. David Solit
    538 Solit
  4. Neil Howard Segal
    139 Segal
  5. Zsofia Kinga Stadler
    198 Stadler
  6. Marc Ladanyi
    1041 Ladanyi
  7. Jinru Shia
    529 Shia
  8. Rona Denit Yaeger
    118 Yaeger
  9. David Hyman
    300 Hyman
  10. Agnes Viale
    215 Viale
  11. Ahmet Zehir
    212 Zehir
  12. Michael Forman Berger
    495 Berger
  13. Efsevia Vakiani
    195 Vakiani
  14. Nancy Kemeny
    432 Kemeny
  15. Jianjiong Gao
    80 Gao
  16. Barry Stephen Taylor
    188 Taylor
  17. Nikolaus D Schultz
    258 Schultz
  18. Daoqi You
    26 You
  19. Aijazuddin Syed
    27 Syed
  20. Jaclyn Frances Hechtman
    160 Hechtman
  21. Sumit   Middha
    77 Middha
  22. Marla   Lipsyc
    4 Lipsyc
  23. Ritika   Kundra
    31 Kundra
  24. Walid Khaled Chatila
    23 Chatila