Prognostic impact of mutation profiling in patients with stage II and III colon cancer

Shen, Yao; Han, Xiaohong; Wang, Jianfei; Wang, Shuai; Yang, Huanming; Lu, Shih-Hsin; Shi, Yuankai

doi:10.1038/srep24310

Cited by 31 publications

(31 citation statements)

References 40 publications

(76 reference statements)

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“…Although a substantial amount of data has been reported on KRAS gene mutations, relative little data has been reported on NRAS mutations. In the present study, NRAS mutations were detected in 1.9% of tumors compared with 4.3% from Taiwan (Chang et al, 2016), 0.9-4.2% from China (Shen et al, 2013;Zhang et al, 2015;Shen et al 2016), 2.7-4.5% from Japan (Ogura et al, 2014;Kawazoe et al, 2015;Osumi et al, 2016), 2.3% from Korea (Lee et al 2015), 3.6-4.6% from Italy (Foltran et al, 2015;Malapelle et al, 2016), and 2.2-5.1% from the United States (Irahara et al, 2010;Vaughn et al, 2011).…”

Section: Discussionmentioning

confidence: 42%

High Frequency of KRAS Codon 146 and FBXW7 Mutations in Thai Patients with Stage II-III Colon Cancer

Korphaisarn

Pongpaibul

Roothumnong

et al. 2019

Asian Pac J Cancer Prev

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Background: KRAS, NRAS, and BRAF gene mutations are the most clinically relevant and frequently reported in colorectal cancer (CRC). Although data on these genes are frequently reported in several counties, data specific to these genes among Thai population are scarce. The aim of this study was to investigate and identify molecular alterations associated with colon cancer in Thai population, and to determine the impact of these genetic aberrations on clinical outcome. Methods:DNA from 108 archived formalin-fixed, paraffin-embedded (FFPE) tissue samples that histologically confirmed adenocarcinoma of stage II-III colon cancer between 2010 and 2012 at Siriraj Hospital (Bangkok, Thailand) were extracted. Gene mutational analysis was performed by next-generation sequencing (NGS) using an Oncomine Solid Tumor DNA kit (Thermo Fisher Scientific, Inc., Waltham, MA, USA). Results:A total of 22 somatic gene mutations were detected. The mutation frequency observed in KRAS, NRAS, BRAF, PIK3CA, and FBXW7 mutations was 47.2%, 1.9%, 1.9%, 12%, and 14.8%, respectively. KRAS mutation codon 12, 13, 59, 61, 117, and 146 mutations were identified in 29.6%, 8.3%, 1.8%, 0.9%, 0.0%, and 8.3%, respectively. KRAS Exon 4 had better DFS compared with Exon 2 and 3. Conclusions:This study is the first to comprehensively report hotspot mutations using NGS in Thai colon cancer patients. The most commonly identified gene mutation frequencies among Thai patients (KRAS, NRAS, BRAF, TP53, and PIK3CA) were similar to the gene mutation frequencies reported in Western population, except for subgroup of KRAS codon 146 and FBXW7 mutations that had a slightly higher frequency.

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Section: Discussionmentioning

confidence: 42%

High Frequency of KRAS Codon 146 and FBXW7 Mutations in Thai Patients with Stage II-III Colon Cancer

Korphaisarn

Pongpaibul

Roothumnong

et al. 2019

Asian Pac J Cancer Prev

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“…But in early stage CRC patients, the prognostic role of BRAF mutations is controversial (Gallo et al, 2019;Smeby et al, 2018). A study conducted by European scholars showed BRAF mutation was an independent prognostic factor in stage II and III CRC (Fariña-Sarasqueta et al, 2010), and a meta-analysis based on randomized clinical trials showed BRAF mutation patients presented poor response to adjuvant chemotherapy (Zhu et al, 2016); however, Chinese scholars demonstrated BRAF mutation did not have prognostic value in stage II and III CRC patients (Shen et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China

Zhang

Wang

et al. 2020

PeerJ

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Objective To investigate the frequency and prognostic role of the human epidermal growth factor receptor 2 gene (HER2) and BRAF V600E gene mutation in Chinese patients with colorectal cancer (CRC). Methods Clinicopathological and survival information from 480 patients with stage I–III CRC were reviewed and recorded. HER2 amplification was analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), BRAF V600E mutation was tested by IHC and Sanger sequencing. The relationship between HER2 and BRAF V600E mutation status and clinicopathological characteristics and outcomes were determined. Results The amplification of HER2 and BRAF V600E mutation were identified in 27 of 480 (5.63%) and 19 of 480 (3.96%) CRC patients, respectively. HER2 amplification significantly correlated with greater bowel wall invasion (P = 0.041) and more advanced TNM stage (I vs. II vs. III; 0 vs 5.78% vs. 7.41%, P = 0.013). Patients suffering from tumors with poor differentiation had a higher incidence rate of BRAF V600E mutation than those with moderate/well differentiation (7.77% vs 2.92%, P = 0.04). HER2 amplification was an independent prognostic factor for worse disease-free survival (DFS) (HR = 2.53, 95% CI: 1.21–5.30, P = 0.014). Conclusion The prevalence of HER2 amplification and BRAF V600E mutation in stage I–III CRC patients in Chinese was 6% and 4%, respectively, and HER2 amplification appeared to be associated with a worse DFS. More comprehensive molecular classification and survival analysis are needed to validate our findings.

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“…Мутации гена PIK3CA (каталитическая субъединица PI3K) присутствуют в 10-20 % всех случаев КРР, чаще проксимальной локализации [22]. Оценить прогностическую роль изолированной мутации PIK3CA трудно, так как до 50 % опухолей несут также мутации BRAF и еще 40 % имеют сопутствующую мутацию RAS [23,24].…”

Section: генетика колоректального ракаunclassified

Prognostic Biomarkers of Gastrointestinal Neoplasia

Щербак¹,

Vologzhanin²,

Гладышев³

et al. 2018

Onkol. koloproktol.

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В эпоху персонализированного лечения онкологи стремятся адаптировать лечение к особенностям конкретного пациента, подчеркивая важность непрерывного поиска точных биомаркеров. Прогностические биомаркеры отражают сложную биологию, которая позволяет раковой опухоли прогрессировать. Внутриопухолевая гетерогенность включает в себя генетическую, эпигенетическую и функциональную. Генетическая внутриопухолевая гетерогенность является следствием клональной эволюции и причиной прогрессирования заболевания. В процессе онкогенеза постоянно накапливаются генетические аберрации, в результате чего раковые опухоли становятся генетически гетерогенными, с множеством сосуществующих клонов, меняющихся с течением времени. При этом специфические мутации ассоциированы с определенными стадиями развития опухоли, которые коррелируют с соответствующими гистопатологическими стадиями заболевания. Многие пациенты с колоректальным раком после резекции опухоли имеют рецидив заболевания, несмотря на проведение адъювантной терапии, в то время как у некоторых пациентов не происходит рецидива, несмотря на отсутствие лечения. Выявление надежных предикторов исхода после резекции остается важной проблемой, поэтому срочно необходимы переоценка существующих критериев и поиск новых прогностических и предиктивных биомаркеров для отбора пациентов, которые могли бы получить пользу от адъювантной химиотерапии. Прогностический биомаркер отражает естественную историю развития опухоли и предоставляет информацию о вероятном исходе и прогнозе независимо от специфического лечения. Предиктивные биомаркеры указывают на чувствительность или резистентность опухоли к определенному лечению. Некоторые биомаркеры могут быть одновременно прогностическими и предиктивными. Генные мутации и эпигенетические аберрации, изменяющие внутриклеточные сигнальные пути, могут быть важными факторами онкогенеза. В этом контексте онкогены, гены-супрессоры опухолей и малые некодирующие молекулы РНК привлекают внимание в качестве потенциальных регуляторов и биомаркеров онкогенеза и оцениваются в клинических исследованиях.

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Prognostic impact of mutation profiling in patients with stage II and III colon cancer

Cited by 31 publications

References 40 publications

High Frequency of KRAS Codon 146 and FBXW7 Mutations in Thai Patients with Stage II-III Colon Cancer

High Frequency of KRAS Codon 146 and FBXW7 Mutations in Thai Patients with Stage II-III Colon Cancer

HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China

Prognostic Biomarkers of Gastrointestinal Neoplasia

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