SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study
Нема приказа
Аутори
Nikolić, AleksandraDespotović, Jovana
Babić, Tamara
Antić, Jadranka
Marković, Srdjan
Krivokapić, Zoran
Radojković, Dragica
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
In colorectal cancer (CRC), inactivation of SMAD4 occurs early in the disease development and SMAD4 represents one of key driver genes in progression and metastasis. Loss of SMAD4 protein expression is a relatively common feature of sporadic colorectal cancers, and it was observed to be even more frequent in tumors of patients with early onset disease and also more frequent in microsatellite stable tumors. Pathogenic variants in the SMAD4 gene are usually missense or nonsense mutations, and they are more frequent in the C-terminal domain. The aim of this study was to perform genetic analysis of SMAD4 C-terminal domain in colorectal cancer patients with early onset disease and microsatellite stable tumors. This pilot study was conducted with a purpose of investigating if such genetic screening strategy would be useful for diagnostic purposes in this specific subgroup of CRC patients. The study was conducted in a selected set of DNA samples extracted from the tumors of CRC patients who h...ad less than 50 years at the time of diagnosis. Genetic analysis of C-terminal domain has encompassed analysis of exons 9, 10, 11 and 12 of the SMAD4 gene by PCR and direct DNA sequencing. Among the twenty analyzed tumor DNAs, one sample was found to harbor a SMAD4 variant: NC_000018.9:g.48591918C gt T; (NM005359.5: c.1081C gt T; Arg361Cys). The variant was discovered in exon 9, affecting the codon 361, which represents a mutational hot spot within the SMAD4 gene. This variant was discovered in homozygous state in the tumor of a 47 yr old female with T3 stage carcinoma of the right colon. Considering the incidence and functional consequences of SMAD4 exon 9 variants, the screening of this region could be a useful low cost strategy for the genetic analysis of colorectal tumors from patients with early onset disease, as well as for susceptibility testing.
Кључне речи:
SMAD4 / pathogenic variant / genetic testing / early onset disease / colorectal cancerИзвор:
Cytology and Genetics, 2022, 56, 3, 273-276Издавач:
- Pleiades Publishing Inc, New York
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
DOI: 10.3103/S0095452722030082
ISSN: 0095-4527
WoS: 000812257100008
Scopus: 2-s2.0-85132109908
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Nikolić, Aleksandra AU - Despotović, Jovana AU - Babić, Tamara AU - Antić, Jadranka AU - Marković, Srdjan AU - Krivokapić, Zoran AU - Radojković, Dragica PY - 2022 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1595 AB - In colorectal cancer (CRC), inactivation of SMAD4 occurs early in the disease development and SMAD4 represents one of key driver genes in progression and metastasis. Loss of SMAD4 protein expression is a relatively common feature of sporadic colorectal cancers, and it was observed to be even more frequent in tumors of patients with early onset disease and also more frequent in microsatellite stable tumors. Pathogenic variants in the SMAD4 gene are usually missense or nonsense mutations, and they are more frequent in the C-terminal domain. The aim of this study was to perform genetic analysis of SMAD4 C-terminal domain in colorectal cancer patients with early onset disease and microsatellite stable tumors. This pilot study was conducted with a purpose of investigating if such genetic screening strategy would be useful for diagnostic purposes in this specific subgroup of CRC patients. The study was conducted in a selected set of DNA samples extracted from the tumors of CRC patients who had less than 50 years at the time of diagnosis. Genetic analysis of C-terminal domain has encompassed analysis of exons 9, 10, 11 and 12 of the SMAD4 gene by PCR and direct DNA sequencing. Among the twenty analyzed tumor DNAs, one sample was found to harbor a SMAD4 variant: NC_000018.9:g.48591918C gt T; (NM005359.5: c.1081C gt T; Arg361Cys). The variant was discovered in exon 9, affecting the codon 361, which represents a mutational hot spot within the SMAD4 gene. This variant was discovered in homozygous state in the tumor of a 47 yr old female with T3 stage carcinoma of the right colon. Considering the incidence and functional consequences of SMAD4 exon 9 variants, the screening of this region could be a useful low cost strategy for the genetic analysis of colorectal tumors from patients with early onset disease, as well as for susceptibility testing. PB - Pleiades Publishing Inc, New York T2 - Cytology and Genetics T1 - SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study EP - 276 IS - 3 SP - 273 VL - 56 DO - 10.3103/S0095452722030082 ER -
@article{ author = "Nikolić, Aleksandra and Despotović, Jovana and Babić, Tamara and Antić, Jadranka and Marković, Srdjan and Krivokapić, Zoran and Radojković, Dragica", year = "2022", abstract = "In colorectal cancer (CRC), inactivation of SMAD4 occurs early in the disease development and SMAD4 represents one of key driver genes in progression and metastasis. Loss of SMAD4 protein expression is a relatively common feature of sporadic colorectal cancers, and it was observed to be even more frequent in tumors of patients with early onset disease and also more frequent in microsatellite stable tumors. Pathogenic variants in the SMAD4 gene are usually missense or nonsense mutations, and they are more frequent in the C-terminal domain. The aim of this study was to perform genetic analysis of SMAD4 C-terminal domain in colorectal cancer patients with early onset disease and microsatellite stable tumors. This pilot study was conducted with a purpose of investigating if such genetic screening strategy would be useful for diagnostic purposes in this specific subgroup of CRC patients. The study was conducted in a selected set of DNA samples extracted from the tumors of CRC patients who had less than 50 years at the time of diagnosis. Genetic analysis of C-terminal domain has encompassed analysis of exons 9, 10, 11 and 12 of the SMAD4 gene by PCR and direct DNA sequencing. Among the twenty analyzed tumor DNAs, one sample was found to harbor a SMAD4 variant: NC_000018.9:g.48591918C gt T; (NM005359.5: c.1081C gt T; Arg361Cys). The variant was discovered in exon 9, affecting the codon 361, which represents a mutational hot spot within the SMAD4 gene. This variant was discovered in homozygous state in the tumor of a 47 yr old female with T3 stage carcinoma of the right colon. Considering the incidence and functional consequences of SMAD4 exon 9 variants, the screening of this region could be a useful low cost strategy for the genetic analysis of colorectal tumors from patients with early onset disease, as well as for susceptibility testing.", publisher = "Pleiades Publishing Inc, New York", journal = "Cytology and Genetics", title = "SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study", pages = "276-273", number = "3", volume = "56", doi = "10.3103/S0095452722030082" }
Nikolić, A., Despotović, J., Babić, T., Antić, J., Marković, S., Krivokapić, Z.,& Radojković, D.. (2022). SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study. in Cytology and Genetics Pleiades Publishing Inc, New York., 56(3), 273-276. https://doi.org/10.3103/S0095452722030082
Nikolić A, Despotović J, Babić T, Antić J, Marković S, Krivokapić Z, Radojković D. SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study. in Cytology and Genetics. 2022;56(3):273-276. doi:10.3103/S0095452722030082 .
Nikolić, Aleksandra, Despotović, Jovana, Babić, Tamara, Antić, Jadranka, Marković, Srdjan, Krivokapić, Zoran, Radojković, Dragica, "SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study" in Cytology and Genetics, 56, no. 3 (2022):273-276, https://doi.org/10.3103/S0095452722030082 . .