Molecular testing for colorectal cancer: Clinical applications

Imyanitov, Evgeny N.; Kuligina, Ekatherina Sh.

doi:10.4251/wjgo.v13.i10.1288

Cited by 10 publications

(11 citation statements)

References 93 publications

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“…CRCs with the BRAF V600E substitution may show aggressive behaviour and could be treated with combined BRAF and EGFR inhibition. Some CRCs have overexpression of the HER2 oncogene that may be analysed by immunohistochemistry and/or in situ hybridisation as they may respond to appropriate targeted therapy [ 22 , 31 ].…”

Section: Rapid Turn-around Cms Classification and Emergence Of Morpho...mentioning

confidence: 99%

Molecular pathological classification of colorectal cancer—an update

Dunne,

Arends

2024

Virchows Arch

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Colorectal cancer (CRC) has a broad range of molecular alterations with two major mechanisms of genomic instability (chromosomal instability and microsatellite instability) and has been subclassified into 4 consensus molecular subtypes (CMS) based on bulk RNA sequence data. Here, we update the molecular pathological classification of CRC with an overview of more recent bulk and single-cell RNA data analysis for development of transcriptional classifiers and risk stratification methods, taking into account the marked inter-tumoural and intra-tumoural heterogeneity of CRC. The importance of the stromal and immune components or tumour microenvironment (TME) to prognosis has emerged from these analyses. Attempts to remove the contribution of the tumour microenvironment and reveal neoplastic-specific transcriptional traits involved identification of the CRC intrinsic subtypes (CRIS). The use of immunohistochemistry and digital pathology to implement classification systems are evolving fields. Conventional adenoma versus serrated polyp pathway transcriptomic analysis and characterisation of canonical LGR5+ crypt base columnar stem cell versus ANXA1+ regenerative stem cell phenotypes emerged as key properties for improved understanding of transcriptional signals involved in molecular subclassification of colorectal cancers. Recently, classification by three pathway-derived subtypes (PDS1-3) has been developed, revealing a continuum of intrinsic biology associated with biological, stem cell, histopathological, and clinical attributes.

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Section: Rapid Turn-around Cms Classification and Emergence Of Morpho...mentioning

confidence: 99%

Molecular pathological classification of colorectal cancer—an update

Dunne,

Arends

2024

Virchows Arch

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“…If tumor progression is detected, targeted intervention can be carried out against the rising clones according to the detected mutation information. Rapid tumor progression can be avoided through timely drug adjustment 22 …”

Section: Implementation Rules For Standardized Management Of Gene Det...mentioning

confidence: 99%

“…Rapid tumor progression can be avoided through timely drug adjustment. 22 In terms of prognosis, patients with ctDNA clearance after surgery have a good long-term prognosis and do not need adjuvant treatment, while patients with residual ctDNA in the blood suggest a high risk of recurrence and need timely systemic treatment to reduce the risk of disease recurrence. Successful systemic treatment will be accompanied by a rapid decrease in ctDNA concentration.…”

Section: Recurrence Monitoringmentioning

confidence: 99%

Expert consensus on standardized management of tumor gene sequencing for cancer patients

Qian

Zhan

et al. 2023

Clinical and Translational Dis

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BackgroundTumour gene detection by next‐generation sequencing (NGS) can comprehensively analyze the molecular characteristics of tumors, and predict drug efficacy and tumor resistance mechanisms through tumour cell models, thereby realizing individualized and precise treatment. Therefore, the whole process of standardized management is required. This consensus aims to refine the standardized management of tumor gene sequencing for cancer patients based on the NGS platform, hoping to provide help for the personalized treatment of cancer patients, and further promoting the development of precision medicine.Methods and resultsStandardized management for tumour gene detection of cancer patients includes patient management before gene testing, during gene testing, and after gene testing. Tumour patients should select appropriate test samples and test content before receiving genetic testing. There should be a clear informed consent statement during the test, a detailed report should be provided after the test, and counseling and monitoring follow‐up should be provided. The management of genetic testing of tumour patients should cover early screening and early diagnosis of tumors, molecular classification and companion diagnosis of tumours, and monitoring of tumour recurrence.ConclusionEffective management and standardized procedures for gene detection of cancer patients, covering the whole process before, during and after detection, will benefit the majority of patients from early screening, personalized diagnosis and treatment, prognosis evaluation and other aspects of cancer, and promote the healthy development of the precision medicine industry.

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“…MSI is particularly common for colorectal carcinomas, with approximately 5-15% of tumors displaying this phenotype. Microsatellite-unstable CRCs often carry mutations leading to MAPK signaling pathway activation, particularly amino acid substitutions in the KRAS, NRAS and BRAF genes [4,7]. Somewhat unexpectedly, MSI-CRCs were repeatedly shown to contain rearrangements in genes encoding receptor tyrosine kinases [2,[8][9][10].…”

Section: Introductionmentioning

confidence: 99%

ALK, ROS1, RET and NTRK1–3 Gene Fusions in Colorectal and Non-Colorectal Microsatellite-Unstable Cancers

Mulkidjan,

Saitova,

Preobrazhenskaya

et al. 2023

IJMS

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This study aimed to conduct a comprehensive analysis of actionable gene rearrangements in tumors with microsatellite instability (MSI). The detection of translocations involved tests for 5′/3′-end expression imbalance, variant-specific PCR and RNA-based next generation sequencing (NGS). Gene fusions were detected in 58/471 (12.3%) colorectal carcinomas (CRCs), 4/69 (5.8%) gastric cancers (GCs) and 3/65 (4.6%) endometrial cancers (ECs) (ALK: 8; RET: 12; NTRK1: 24; NTRK2: 2; NTRK3: 19), while none of these alterations were observed in five cervical carcinomas (CCs), four pancreatic cancers (PanCs), three cholangiocarcinomas (ChCs) and two ovarian cancers (OCs). The highest frequency of gene rearrangements was seen in KRAS/NRAS/BRAF wild-type colorectal carcinomas (53/204 (26%)). Surprisingly, as many as 5/267 (1.9%) KRAS/NRAS/BRAF-mutated CRCs also carried tyrosine kinase fusions. Droplet digital PCR (ddPCR) analysis of the fraction of KRAS/NRAS/BRAF mutated gene copies in kinase-rearranged tumors indicated that there was simultaneous co-occurrence of two activating events in cancer cells, but not genetic mosaicism. CRC patients aged above 50 years had a strikingly higher frequency of translocations as compared to younger subjects (56/365 (15.3%) vs. 2/106 (1.9%), p = 0.002), and this difference was particularly pronounced for tumors with normal KRAS/NRAS/BRAF status (52/150 (34.7%) vs. 1/54 (1.9%), p = 0.001). There were no instances of MSI in 56 non-colorectal tumors carrying ALK, ROS1, RET or NTRK1 rearrangements. An analysis of tyrosine kinase gene translocations is particularly feasible in KRAS/NRAS/BRAF wild-type microsatellite-unstable CRCs, although other categories of tumors with MSI also demonstrate moderate occurrence of these events.

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Molecular testing for colorectal cancer: Clinical applications

Cited by 10 publications

References 93 publications

Molecular pathological classification of colorectal cancer—an update

Molecular pathological classification of colorectal cancer—an update

Expert consensus on standardized management of tumor gene sequencing for cancer patients

ALK, ROS1, RET and NTRK1–3 Gene Fusions in Colorectal and Non-Colorectal Microsatellite-Unstable Cancers

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