Novel recurrently mutated genes in African American colon cancers

Guda, Kishore; Veigl, Martina L.; Varadan, Vinay; Nosrati, Arman; Ravi, Lakshmeswari; Lutterbaugh, James; Beard, Lydia; Willson, James K.V.; Sedwick, W. David; Wang, Benlian; Molyneaux, Neil; Miron, Alexander; Adams, Mark D.; Elston, Robert C.; Markowitz, Sanford D.; Willis, Joseph E.

doi:10.1073/pnas.1417064112

Cited by 115 publications

(103 citation statements)

References 27 publications

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“…Black patients display a higher frequency of KRAS mutations in tumors, increasing the aggressiveness of the CRC [87]. Mutations in the driver genes EPHA6 and FLCN were found exclusively in Black CRCs, suggesting a unique behavior modifying role for these CRCs [88]. Another study identified novel somatic alterations in well-known CRC genes ( APC, BRAF, KRAS , and PIK3CA ) among Blacks [89].…”

Section: Introductionmentioning

confidence: 99%

Racial Disparity in Gastrointestinal Cancer Risk

et al. 2017

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Cancer from the gastrointestinal tract and its associated excretory organs will occur in over 300,000 Americans in 2017, with colorectal cancer responsible for over forty percent of that burden; there will be over 150,000 deaths from this group of cancers in the same time period. Disparities among subgroups related to these cancers’ incidence and mortality exist. The epidemiology and risk factors associated with each cancer bear out differences for racial groups in the United States. Esophageal adenocarcinoma is more frequent in Non-Hispanic Whites, whereas esophageal squamous cell carcinoma with risk factors of tobacco and alcohol is more frequent among Blacks. Liver cancer has been most frequent among Asian/Pacific Islanders chiefly due to hepatitis B vertical transmission, but other racial groups show increasing rates due to hepatitis C and emergence of cirrhosis from non-alcoholic fatty liver disease. Gastric cancer incidence remains highest among Asian/Pacific Islanders likely due to gene-environment interaction. In addition to esophageal squamous cell carcinoma, cancers of the small bowel, pancreas and colorectum show the highest rates among Blacks, where the explanations for the disparity are not as obvious and are likely multifactorial, including socio-economic and health care access, treatment and prevention (vaccination and screening) differences, dietary and composition of the gut microbiome, as well as biological and genetic influences. Cognizance of these disparities in gastrointestinal cancer risk, as well as approaches that apply precision medicine methods to populations with the increased risk, may reduce the observed disparities for digestive cancers.

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Section: Introductionmentioning

confidence: 99%

Racial Disparity in Gastrointestinal Cancer Risk

et al. 2017

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“…[11][12][13] It is known that treatment based on KRAS status has revolutionized personalized medicine. Similarly, mutations in BRAF that have been observed in several sessile serrated adenomas also rule out the diagnosis of Lynch syndrome.…”

Section: Introductionmentioning

confidence: 99%

Molecular markers and pathway analysis of colorectal carcinoma in the Middle East

Beg

Siraj

Prabhakaran

et al. 2015

Cancer

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BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the world. A newly proposed integrated pathway comprising traditional, alternate, and serrated pathways by genetic and epigenetic factors was defined recently and hypothesized to play a role in the pathogenesis of CRC; however, to the authors' knowledge, there is a paucity of information regarding these proposed molecular pathways in different ethnic groups. METHODS: Molecular characterization of 770 CRC specimens was performed for microsatellite instability, BRAF, and KRAS by polymerase chain reaction and 500 cases for CpG island methylator phenotype (CIMP) high phenotype by MethyLight technology. Tumors were assigned to different molecular pathways and examined for clinicopathological correlation and survival analysis. RESULTS: The traditional pathway constituted 33.4% of CRC cases, the alternate pathway comprised 11.6%, and the serrated molecular pathway accounted for only 0.8% of Middle Eastern CRC cases. Approximately 54.2% of CRC cases did not qualify to fit into any pathway and thus were designated as an unassigned group. Molecular pathways were found to be significantly associated with tumor site and grade. A subset of cases with an uncategorized pathway demonstrated a significant survival difference (P 5 .0079). CONCLUSIONS: The serrated pathway was found to account for a very low percentage of the CRC patient cohort in the current study. The unassigned group accounted for the majority of Middle Eastern CRC cases, and therefore methods of CRC pathway analysis might not be applicable to this ethnic group. The current study demonstrates the need to unravel the molecular genetic basis of this disease to further subcategorize these CRC cases. It also identifies a need for further studies on different populations for a better understanding of their exact role and incidence. Cancer 2015;121:3799-808.

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“…Tumor progression in CRC is a multi-step process that involves alterations at the genetic and epigenetic level (31)(32)(33). Accumulated evidence has led to the view that miRNAs serve important functions in cancer formation and through the regulation of tumor cell proliferation, cycle, apoptosis, metastasis and angiogenesis (34-36).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑539 inhibits colorectal cancer progression by directly targeting SOX4

Zhao

Zhang

2018

Oncol Lett

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Abstract. Colorectal cancer (CRC) is the third most prevalent cancer and the fourth most common cause of cancer-associated mortality in males and females globally. Aberrant expression of microRNA-539 (miR-539) has been reported in multiple types of cancer. However, miR-539 expression, function and underlying mechanisms have not been clearly elucidated in CRC. In the present study, miR-539 expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in CRC tissues and cell lines. The effects of miR-539 on CRC cells were further examined in in vitro studies. In addition, the direct targets of miR-539 in CRC were investigated using bioinformatics, luciferase reporter assays, RT-qPCR and western blotting. miR-539 was revealed to be significantly downregulated in CRC cell lines and tissues. Decreased miR-539 expression was associated with lymph node metastasis and tumor-node-metastasis stage in patients with CRC. Functional assays revealed that the rescue of miR-539 expression attenuated CRC cell proliferation and invasion in vitro. Additionally, SRY-box 4 (SOX4) was validated as a direct target gene of miR-539 in CRC. Furthermore, SOX4 was revealed to be upregulated in CRC tissues at the mRNA and protein level. A significant negative correlation between miR-539 and SOX4 mRNA expression levels was observed in CRC tissues. Furthermore, upregulation of SOX4 partially restored the tumor suppressive effects of miR-539 on CRC cell proliferation and invasion. Taken together, this suggests that miR-539 may serve tumor-suppressive functions in CRC during the process of malignant transformation, by directly targeting SOX4. miR-539/SOX4-based targeted therapy may represent a potential novel treatment for patients with CRC.

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Novel recurrently mutated genes in African American colon cancers

Cited by 115 publications

References 27 publications

Racial Disparity in Gastrointestinal Cancer Risk

Racial Disparity in Gastrointestinal Cancer Risk

Molecular markers and pathway analysis of colorectal carcinoma in the Middle East

MicroRNA‑539 inhibits colorectal cancer progression by directly targeting SOX4

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