Clinical significance and prognostic relevance of KRAS, BRAF, PI3K and TP53 genetic mutation analysis for resectable and unresectable colorectal liver metastases: A systematic review of the current evidence

Tsilimigras, Diamantis I.; Ntanasis‐Stathopoulos, Ioannis; Bagante, Fabio; Moris, Demetrios; Cloyd, Jordan M.; Spartalis, Eleftherios; Pawlik, Timothy M.

doi:10.1016/j.suronc.2018.05.012

Cited by 148 publications

(142 citation statements)

References 91 publications

Supporting

Mentioning

125

Contrasting

Order By: Relevance

“…35 given the complex interactions of tumor location, MSI status, and type of chemotherapy; this will need to be further evaluated in the context of each primary tumor type. 16,37,38 The deleterious biological ramifications of SMAD4 mutation previously reported include aggressive in vitro/in vivo phenotype, late event in tumor clonality, high-frequency association with mucinous histology, and association with advanced/metastatic tumor stage. [39][40][41][42][43][44] The cellular mechanism is due to the loss of autocrine TGFβ suppressive effects, resulting in uncontrolled proliferation, loss of apoptosis, and epithelial to | 1111 mesenchymal transition progression.…”

Section: Rate Of Actionable Mutationsmentioning

confidence: 99%

“…[13][14][15] The concept of leveraging mutation profiling for metastatic CRC surgery has been recently reported in the setting of hepatectomy with evidence that BRAF predicts worst overall outcome and RAS mutations portend a worse outcome, although this relationship is impacted by the type of resection and margin status. [16][17][18][19][20] Extended mutation profiling (50-gene panels) has not been explored for identifying mutations and their frequency in GIM-PM, nor has probing for mutations shared across multiple tumor types been investigated. LGMCP patient was excluded due to synchronous colon cancer, and one…”

mentioning

confidence: 99%

See 1 more Smart Citation

Investigating the utility of extended mutation analysis in gastrointestinal peritoneal metastasis

Foster

Patel

Zhang

et al. 2020

Journal of Surgical Oncology

View full text Add to dashboard Cite

Background and Objectives: Outcomes for gastrointestinal peritoneal metastases (GI-PM) are worse compared to systemic metastases, with a paucity of data exploring extended mutation profiling. An exploratory mutation analysis in GI-PMs was performed as a "proof of concept" of potential predictive values of profiling in GI-PM and rates of actionable mutations. Methods: The study included 40 GI-PM patients: 14 low-grade mucinous carcinoma peritonei and 26 HG-PM (12 colons, 10 appendix, 4 small bowels). Demographics, histologies, peritoneal cancer indexes, cytoreduction scores, and survival data were collected. NGS 50-gene mutation profiling was performed on 38 specimens. The association of mutations with survival was evaluated in high-grade PM. Results: KRAS, TP53, and SMAD4 mutations were observed in 61%, 29%, and 8% of cases across all tumor histologies. In 66% cases >1 mutations occurred, associated with decreased survival in HG-PM: 32 vs 73 months, P = .03. TP53 or SMAD4 mutations were associated with decreased survival in HG-PM: 22 vs 48 months, P = .02. Actionable mutations were detected in 70%. Conclusion: Actionable mutations were detected at high rates. GI-PMs have similar mutational profiles and TP53, SMAD4, and/or >1 mutation were associate with decreased survival in HG-PM. This data supports the concept of the extended mutation profiling utility in GI-PM warranting further investigation.

show abstract

Section: Rate Of Actionable Mutationsmentioning

confidence: 99%

mentioning

confidence: 99%

Investigating the utility of extended mutation analysis in gastrointestinal peritoneal metastasis

Foster

Patel

Zhang

et al. 2020

Journal of Surgical Oncology

View full text Add to dashboard Cite

show abstract

“…Several research groups have provided evidence that two proto-oncogenes, KRAS and BRAF , are associated with resistance to chemotherapy and poor prognosis [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ], as confirmed by the survival analysis of the BRAF mutated CRCLM included in the TCGA cohort ( Figure 4 B).…”

Section: Resultsmentioning

confidence: 83%

Molecular and Immunohistochemical Markers with Prognostic and Predictive Significance in Liver Metastases from Colorectal Carcinoma

Lopez

Boggio

Ferrero

et al. 2018

IJMS

View full text Add to dashboard Cite

Despite the significant recent achievements in the diagnosis and treatment of colorectal cancer (CRC), the prognosis of these patients has currently plateaued. During the past few years, the opportunity to consider multiple treatment modalities (including surgery and other locoregional treatments, systemic therapy, and targeted therapy) led to the research of novel prognostic and predictive biomarkers in CRC liver metastases (CRCLM) patients. In this review, we seek to describe the current state of knowledge of CRCLM biomarkers and to outline impending clinical perspectives, in particular focusing on the cutting-edge tools available for their characterization.

show abstract

“…It is reported that PIK3CA mutation is related to older age, proximal tumors, mucinous histology, and KRAS mutation [17,18]. However, these studies do not stratify CRC cases by MMR status, since pMMR and dMMR tumors show distinct differences in clinicopathologic and molecular characteristics.…”

Section: Discussionmentioning

confidence: 97%

Prevalence and characteristics of PIK3CA mutation in mismatch repair-deficient colorectal cancer

Qiu

Dong

et al. 2020

J. Cancer

View full text Add to dashboard Cite

Background: Chromosomal instability (CIN) and microsatellite instability (MSI) account for the major causes of colorectal cancer (CRC). As an important component of the CIN pathway, PIK3CA mutation is a negative prognostic factor in CRC. However, the relationship between PIK3CA mutation and mismatch repair (MMR) status has not been well clarified. Methods: MMR status was determined by immunohistochemical assay. KRAS, NRAS, BRAF, PIK3CA and TP53 mutations were comparatively analyzed in 424 MMR-proficient (pMMR) and 104 MMR-deficient (dMMR) CRC tumors using next-generation sequencing (NGS). Results: PIK3CA mutation was more commonly mutated in dMMR tumors. PIK3CA mutation less commonly coexisted with KRAS/NRAS/BRAF and TP53 mutations, but more likely coexisted with HER2 and PTCH1 mutations in dMMR tumors compared with pMMR tumors. In tumors with concurrent RAS/BRAF and PIK3CA mutations, PIK3CA and RAS/BRAF mutant allele frequencies (MAFs) were highly concordant in dMMR tumors, whereas PIK3CA MAFs were significantly lower than the corresponding RAS/BRAF MAFs in pMMR tumors, implying that PIK3CA mutation may occur in the early stage of dMMR CRC. Conclusions: The molecular pathogenesis is different between dMMR and pMMR tumors with PIK3CA mutation in CRC. PIK3CA mutation may act as a clonally dominant truncal mutation in dMMR CRC. Thus, combination of PIK3CA mutation and MMR status might determine a specific group of CRC to select treatment or elevate prognosis.

show abstract

Clinical significance and prognostic relevance of KRAS, BRAF, PI3K and TP53 genetic mutation analysis for resectable and unresectable colorectal liver metastases: A systematic review of the current evidence

Cited by 148 publications

References 91 publications

Investigating the utility of extended mutation analysis in gastrointestinal peritoneal metastasis

Investigating the utility of extended mutation analysis in gastrointestinal peritoneal metastasis

Molecular and Immunohistochemical Markers with Prognostic and Predictive Significance in Liver Metastases from Colorectal Carcinoma

Prevalence and characteristics of PIK3CA mutation in mismatch repair-deficient colorectal cancer

Contact Info

Product

Resources

About