TY - JOUR
T1 - Association of microsatellite instability (MSI) status with the 5-year outcome and genetic ancestry in a large Brazilian cohort of colorectal cancer
AU - Berardinelli, Gustavo Noriz
AU - Durães, Ronílson
AU - Mafra da Costa, Allini
AU - Bragagnoli, Arinilda
AU - Antônio de Oliveira, Marco
AU - Pereira, Rui
AU - Scapulatempo-Neto, Cristovam
AU - Guimarães, Denise Peixoto
AU - Reis, Rui Manuel
N1 - Funding Information:
This study was partially supported by Barretos Cancer Hospital Internal Research Funds (PAIP) of participant authors and the Public Ministry of Labor – Campinas, São Paulo (Research, Prevention, and Education of Occupational Cancer). RMR was the recipient of a National Council of Technological and Scientific Development (CNPq) scholarship. AMC had financial support from the São Paulo Government (São Paulo Research Foundation – FAPESP) through the grants numbers 2019/21722–0 and 2018/22097–0.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to European Society of Human Genetics.
PY - 2022/7
Y1 - 2022/7
N2 - Colorectal cancer (CRC) has a high incidence and mortality worldwide. Microsatellite instability (MSI) is crucial in CRC, with distinct molecular and clinicopathological features in patients. Nowadays, it is a predictive marker for immunotherapy. We proposed to evaluate the 5-year outcome of MSI status in 1002 Brazilian CRC, and associate it with genetic ancestry, molecular and clinicopathological features. MSI evaluation was performed using molecular markers. MSI+ tumors were analyzed for alterations in 23 MSI-targeted genes. Genetic ancestry was evaluated using an Ancestry-Informative markers panel. MSI status was analyzed in relation to CRC specific survival and other clinical and genetic variables. MSI+ status was observed in 10.5% of cases. MSI+ status was significantly associated with the anatomic site right colon, mucinous histological type, clinical stage II, histological grade III/undifferentiated, no recurrence of disease, and live cases without cancer. No association of MSI status with genetic ancestry components was observed. MSI-targeted genes analyses showed the most frequently altered genes: ATM, EGFR, MRE11, ROCK1, and TGFBRII. There was a statistically significant difference in cancer-specific survival between cases according to MSI status. This study constitutes the most comprehensive analyses of the MSI impact on the Brazilian CRC. MSI+ frequency in Brazilian CRC agreed with the literature and was associated with several clinicopathological features related with less aggressive tumors, independently of their genetic ancestry.
AB - Colorectal cancer (CRC) has a high incidence and mortality worldwide. Microsatellite instability (MSI) is crucial in CRC, with distinct molecular and clinicopathological features in patients. Nowadays, it is a predictive marker for immunotherapy. We proposed to evaluate the 5-year outcome of MSI status in 1002 Brazilian CRC, and associate it with genetic ancestry, molecular and clinicopathological features. MSI evaluation was performed using molecular markers. MSI+ tumors were analyzed for alterations in 23 MSI-targeted genes. Genetic ancestry was evaluated using an Ancestry-Informative markers panel. MSI status was analyzed in relation to CRC specific survival and other clinical and genetic variables. MSI+ status was observed in 10.5% of cases. MSI+ status was significantly associated with the anatomic site right colon, mucinous histological type, clinical stage II, histological grade III/undifferentiated, no recurrence of disease, and live cases without cancer. No association of MSI status with genetic ancestry components was observed. MSI-targeted genes analyses showed the most frequently altered genes: ATM, EGFR, MRE11, ROCK1, and TGFBRII. There was a statistically significant difference in cancer-specific survival between cases according to MSI status. This study constitutes the most comprehensive analyses of the MSI impact on the Brazilian CRC. MSI+ frequency in Brazilian CRC agreed with the literature and was associated with several clinicopathological features related with less aggressive tumors, independently of their genetic ancestry.
UR - https://www.scopus.com/pages/publications/85128904495
UR - https://pubmed.ncbi.nlm.nih.gov/35474354
U2 - 10.1038/s41431-022-01104-y
DO - 10.1038/s41431-022-01104-y
M3 - Article
C2 - 35474354
AN - SCOPUS:85128904495
SN - 1018-4813
VL - 30
SP - 824
EP - 832
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 7
ER -