Molecular and phenotypic profiling of colorectal cancer patients in West Africa reveals biological insights

被引:35
作者
Alatise, Olusegun Isaac [1 ]
Knapp, Gregory C. [2 ,20 ]
Sharma, Avinash [2 ]
Chatila, Walid K. [3 ,4 ,5 ]
Arowolo, Olukayode A. [1 ]
Olasehinde, Olalekan [1 ]
Famurewa, Olusola C. [1 ]
Omisore, Adeleye D. [1 ]
Komolafe, Akinwumi O. [1 ]
Olaofe, Olaejinrinde O. [1 ]
Katung, Aba I. [6 ]
Ibikunle, David E. [6 ]
Egberongbe, Adedeji A. [6 ]
Olatoke, Samuel A. [7 ]
Agodirin, Sulaiman O. [7 ]
Adesiyun, Olusola A. [7 ]
Adeyeye, Ademola [7 ]
Kolawole, Oladapo A. [8 ]
Olakanmi, Akinwumi O. [9 ]
Arora, Kanika [3 ,4 ]
Constable, Jeremy [2 ]
Shah, Ronak [3 ,4 ]
Basunia, Azfar [3 ,4 ]
Sylvester, Brooke [4 ]
Wu, Chao [4 ]
Weiser, Martin R. [10 ]
Seier, Ken [11 ]
Gonen, Mithat [11 ]
Stadler, Zsofia K. [12 ,13 ,14 ]
Kemel, Yelena [15 ]
Vakiani, Efsevia [4 ]
Berger, Michael F. [4 ]
Chan, Timothy A. [4 ,16 ]
Solit, David B. [4 ]
Shia, Jinru [17 ]
Sanchez-Vega, Francisco [4 ]
Schultz, Nikolaus [4 ]
Brennan, Murray [18 ]
Smith, J. Joshua [4 ,10 ]
Kingham, T. Peter [19 ]
机构
[1] Obafemi Awolowo Univ, Coll Hlth Sci, Fac Clin Sci, Ife, Nigeria
[2] Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA
[3] Mem Sloan Kettering Canc Ctr, Marie Jose & Henry R Kravis Ctr Mol Oncol, 1275 York Ave, New York, NY 10021 USA
[4] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA
[5] Weill Cornell Med Coll, TriInst Program Computat Biol & Med, New York, NY USA
[6] Fed Med Ctr, Owo, Ondo State, Nigeria
[7] Univ Ilorin Teaching Hosp, Dept Surg, Ilorin, Nigeria
[8] Ladoke Akintola Univ Technol, Dept Surg, Ogbomosho, Oyo State, Nigeria
[9] Univ Med Sci, Dept Surg, Ondo, Ondo State, Nigeria
[10] Mem Sloan Kettering Canc Ctr, Colorectal Serv, Dept Surg, 1275 York Ave, New York, NY 10021 USA
[11] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA
[12] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, 1275 York Ave, New York, NY 10021 USA
[13] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA
[14] Mem Sloan Kettering Canc Ctr, Gastrointestinal Oncol Serv, Dept Med, New York, NY USA
[15] Mem Sloan Kettering Canc Ctr, Niehaus Ctr Inherited Canc Gen, 1275 York Ave, New York, NY 10021 USA
[16] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10021 USA
[17] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA
[18] Mem Sloan Kettering Canc Ctr, Bobst Int Ctr, 1275 York Ave, New York, NY 10021 USA
[19] Mem Sloan Kettering Canc Ctr, Dept Surg, Hepatopancreatobiliary Serv, 1275 York Ave, New York, NY 10021 USA
[20] Dalhousie Univ, Dept Surg, Div Gen Surg, Halifax, NS, Canada
关键词
MISMATCH REPAIR DEFICIENCY; MICROSATELLITE INSTABILITY; LANDSCAPE; COLON;
D O I
10.1038/s41467-021-27106-w
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is vital to addressing the regions rising burden of disease. Tissue from unselected Nigerian patients was analyzed with a multigene, next-generation sequencing assay. The rate of microsatellite instability is significantly higher among Nigerian CRC patients (28.1%) than patients from The Cancer Genome Atlas (TCGA, 14.2%) and Memorial Sloan Kettering Cancer Center (MSKCC, 8.5%, P < 0.001). In microsatellite-stable cases, tumors from Nigerian patients are less likely to have APC mutations (39.1% vs. 76.0% MSKCC P < 0.001) and WNT pathway alterations (47.8% vs. 81.9% MSKCC, P < 0.001); whereas RAS pathway alteration is more prevalent (76.1% vs. 59.6%, P = 0.03). Nigerian CRC patients are also younger and more likely to present with rectal disease (50.8% vs. 33.7% MSKCC, P < 0.001). The findings suggest a unique biology of CRC in Nigeria, which emphasizes the need for regional data to guide diagnostic and treatment approaches for patients in West Africa. Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is important for early detection and treatment. Here, the authors use a multigene next-generation sequencing panel to identify genomic differences in Nigerian CRCs compared to those from TCGA and MSKCC cohorts.
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