Role of Genetic Ancestry in 1,002 Brazilian Colorectal Cancer Patients From Barretos Cancer Hospital

Durães, Ronilson Oliveira; Berardinelli, Gustavo Nóriz; Costa, Allini Mafra da; Scapulatempo‐Neto, Cristovam; Pereira, Rui; Oliveira, Marco Antônio de; Guimarães, Denise Peixoto; Reis, Rui Manuel

doi:10.3389/fonc.2020.00145

Cited by 19 publications

(27 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous studies have reported that polyps and colorectal cancer are more frequent among African Americans than non-Hispanic Whites [ 64 – 66 ]. In the present study, as expected [ 30 , 67 , 68 ], we observed a high heterogeneity of the ancestry proportions in our study population, yet, we did not find any difference between genetic ancestry and the groups of precursor lesions evaluated. This result could be due to the small number of cases within each group analyzed.…”

Section: Discussionsupporting

confidence: 82%

“…The genetic ancestry of 81 patients with colorectal precursor lesions with available blood was determined by 46 autosomal ancestry informative markers (AIMs), which consist of insertion-deletion polymorphisms (INDELs) as described [ 30 ]. A multiplex PCR was followed by a fragment analysis performed by ABI 3500xL Genetic Analyzer (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Somatic targeted mutation profiling of colorectal cancer precursor lesions

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background Most colorectal cancers (CRC) arise from precursor lesions. This study aimed to characterize the mutation profile of colorectal cancer precursor lesions in a Brazilian population. Methods In total, 90 formalin-fixed paraffin-embedded colorectal precursor lesions, including 67 adenomas, 7 sessile serrated lesions, and 16 hyperplastic polyps, were analyzed by next-generation sequencing using a panel of 50 oncogenes and tumor suppressor genes. The genetic ancestry of the patients was estimated. Results Somatic driver mutations were identified in 66.7% of cases, including alterations in APC (32.2%), TP53 (20.0%), KRAS (18.9%), BRAF (13.3%) and EGFR (7.8%). Adenomas displayed a higher number of mutations, mainly in APC, compared to serrated polyps (73.1% vs. 47.8%, p = 0.026). Advanced adenomas had a significantly higher frequency of mutation in KRAS and a high overall mutation rate than early adenomas (92.9% vs. 59%, p = 0.006). A high degree of ancestry admixture was observed in the population studied, with a predominance of European components (mean of 73%) followed by African (mean of 11.3%). No association between genetic ancestry and type of lesions was found. The mutation profile of Brazilian colorectal precursor lesions exhibits alteration in APC, KRAS, TP53, and BRAF at different frequencies according to lesion type. Conclusions These results bestow the knowledge of CRC's biologic history and support the potential of these biomarkers for precursor lesions detection in CRC screening of the Brazilian population.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Methodsmentioning

confidence: 99%

Somatic targeted mutation profiling of colorectal cancer precursor lesions

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, several studies were conducted on this patient population to determine their genetic-based ethnicity and correlate their ethnicity with clinical characteristics. These studies observed considerable admixture in the genetic composition 35 – 38 .…”

Section: Methodsmentioning

confidence: 96%

Cutaneous and acral melanoma cross-OMICs reveals prognostic cancer drivers associated with pathobiology and ultraviolet exposure

et al. 2022

Self Cite

View full text Add to dashboard Cite

Ultraviolet radiation (UV) is causally linked to cutaneous melanoma, yet the underlying epigenetic mechanisms, known as molecular sensors of exposure, have not been characterized in clinical biospecimens. Here, we integrate clinical, epigenome (DNA methylome), genome and transcriptome profiling of 112 cutaneous melanoma from two multi-ethnic cohorts. We identify UV-related alterations in regulatory regions and immunological pathways, with multi-OMICs cancer driver potential affecting patient survival. TAPBP, the top gene, is critically involved in immune function and encompasses several UV-altered methylation sites that were validated by targeted sequencing, providing cost-effective opportunities for clinical application. The DNA methylome also reveals non UV-related aberrations underlying pathological differences between the cutaneous and 17 acral melanomas. Unsupervised epigenomic mapping demonstrated that non UV-mutant cutaneous melanoma more closely resembles acral rather than UV-exposed cutaneous melanoma, with the latter showing better patient prognosis than the other two forms. These gene-environment interactions reveal translationally impactful mechanisms in melanomagenesis.

show abstract

“…In addition, several studies were conducted on this patient population to determine their genetic-based ethnicity and correlate their ancestry with clinical characteristics. These studies observed considerable admixture in the genetic composition [35][36][37][38] .…”

Section: Patient Eligibility Biospecimen and Clinical Datamentioning

confidence: 96%

Cutaneous and acral melanoma cross-OMICs reveals prognostic cancer drivers associated with pathobiology and ultraviolet exposure

Vicente

Novoloaca

Cahais

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Ultraviolet radiation (UV) is causally linked to cutaneous melanoma, yet the underlying epigenetic mechanisms, known as molecular sensors of exposure, have never been characterized in clinical biospecimen. Here, we integrate clinical and epigenome (DNA methylome), genome and transcriptome profiling of 112 cutaneous melanoma from two multi-ethnic cohorts. We identify UV-related alterations in regulatory regions and immunological pathways, with multi-OMICs cancer driver potential affecting patient survival. TAPBP, the top gene, is critically involved in immune function and encompasses several UV-altered methylation sites that were validated by targeted sequencing, providing cost-effective opportunities for clinical application. The DNA methylome also reveals non UV-related aberrations underlying pathological differences between the cutaneous and 17 acral melanomas. Unsupervised epigenomic mapping demonstrated that non UV-mutant cutaneous melanoma more closely resembles acral rather than UV-exposed cutaneous melanoma, with the latter showing better patient prognosis than the other two forms. These gene-environment interactions reveal translationally impactful mechanisms in melanomagenesis.

show abstract

Role of Genetic Ancestry in 1,002 Brazilian Colorectal Cancer Patients From Barretos Cancer Hospital

Cited by 19 publications

References 58 publications

Somatic targeted mutation profiling of colorectal cancer precursor lesions

Somatic targeted mutation profiling of colorectal cancer precursor lesions

Cutaneous and acral melanoma cross-OMICs reveals prognostic cancer drivers associated with pathobiology and ultraviolet exposure

Cutaneous and acral melanoma cross-OMICs reveals prognostic cancer drivers associated with pathobiology and ultraviolet exposure

Contact Info

Product

Resources

About