MSI Analysis in Solid and Liquid Biopsies of Gastroesophageal Adenocarcinoma Patients: A Molecular Approach

Boldrin, Elisa; Piano, Maria Assunta; Alfieri, Rita; Mazza, M.; Vassallo, Lorenzo; Scapinello, Antonio; Pilati, Pierluigi; Curtarello, Matteo

doi:10.3390/ijms22147244

Cited by 9 publications

(15 citation statements)

References 32 publications

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“…Similarly, on the basis of recent molecular classification of gastric adenocarcinoma (GAC) proposed by The Cancer Genome Atlas Research Network, Boldrin et al compared the analytical performance of different PCR-based approaches (multiplex PCR, real-time PCR and droplet digital PCR) for the detection of MSI status from liquid biopsy specimens previously tested on corresponding tissue specimens. Overall, data confirmed the molecular analysis in liquid biopsy samples as a reliable integrating approach for MSI status evaluation and the digital droplet PCR as the most feasible technique in the analysis of MSI profile from liquid biopsy specimens (59).…”

Section: Detection Of Msi As a Predictive And Prognostic Biomarkersupporting

confidence: 60%

Microsatellite Instable Colorectal Adenocarcinoma Diagnostics: The Advent of Liquid Biopsy Approaches

et al. 2022

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The introduction of immunotherapy has revolutionized the oncological targeted therapy paradigm. Microsatellite instability (MSI) identifies a subgroup of colorectal cancers (CRCs) which respond to treatment with immune checkpoint inhibitors. Tissue biopsy is currently the gold standard for the assessment of MSI/Mismatch Repair deficiency (MMRd) by means immunohistochemistry or molecular assays. However, the application of liquid biopsy in the clinic may help to overcome several limitations of tissue analysis and may provide great benefit to the diagnostic scenario and therapeutic decision-making process. In the context of MSI/MMRd CRC, the use of liquid biopsy may allow to establish MSI/MMR status if tissue sampling cannot be performed or in case of discordant tissue biopsies. Liquid biopsy may also become a powerful tool to monitor treatment response and the onset resistance to immunotherapy over time and to stratify of MSI/MMRd patients according to their risk of relapse and metastases. The aim of this review is to summarize the main technical aspects and clinical applications, the benefits, and limitations of the use of liquid biopsy in MSI/MMRd colorectal cancer patients.

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Section: Detection Of Msi As a Predictive And Prognostic Biomarkersupporting

confidence: 60%

Microsatellite Instable Colorectal Adenocarcinoma Diagnostics: The Advent of Liquid Biopsy Approaches

et al. 2022

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“…Both amplicon sequencing [ 55 ] and target-capture/deep-sequencing approaches [ 48 ] have been used to identify tumour DNA within urine cfDNA at the point of diagnosis, and capture approaches have since been adapted to incorporate MSI markers (e.g., [ 56 , 57 , 58 ]). ddPCR-based MSI assays [ 59 , 60 ] have also recently been developed that are potentially simpler and more cost-effective options for early detection of LS-derived tumours. Here, mPCR identified a clear MSI signal from an LS patient’s UTUC prior to surgery, with approximately 70% of preop cfDNA being tumour-derived.…”

Section: Discussionmentioning

confidence: 99%

“…Much larger numbers of UC and EC samples from LS patients will need to be analysed, and/or patient groups at increased risk of developing these cancers, such as MSH2 -variant carriers for UTUCs [ 2 ] and patients presenting with post-menopausal bleeding for EC [ 37 ]. In addition, the mPCR assay would benefit from further refinement, as the lower limit of detection (LLoD) is likely to be similar to the parent assay (3% tumour DNA [ 31 ]), much higher than the LLoD of both capture/deep sequencing (e.g., ~0.4% [ 58 ]) and ddPCR (~0.2%, [ 60 ]). This could be improved by using more sophisticated data analysis methods (e.g., [ 32 ]), using a high-fidelity polymerase in the first round of PCR, and by increasing marker read depth to enable analysis of smSequences rather than raw reads.…”

Section: Discussionmentioning

confidence: 99%

Detection of Microsatellite Instability in Colonoscopic Biopsies and Postal Urine Samples from Lynch Syndrome Cancer Patients Using a Multiplex PCR Assay

Phelps

Gallon

Hayes

et al. 2022

Cancers

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Identification of mismatch repair (MMR)-deficient colorectal cancers (CRCs) is recommended for Lynch syndrome (LS) screening, and supports targeting of immune checkpoint inhibitors. Microsatellite instability (MSI) analysis is commonly used to test for MMR deficiency. Testing biopsies prior to tumour resection can inform surgical and therapeutic decisions, but can be limited by DNA quantity. MSI analysis of voided urine could also provide much needed surveillance for genitourinary tract cancers in LS. Here, we reconfigure an existing molecular inversion probe-based MSI and BRAF c.1799T > A assay to a multiplex PCR (mPCR) format, and demonstrate that it can sample >140 unique molecules per marker from <1 ng of DNA and classify CRCs with 96–100% sensitivity and specificity. We also show that it can detect increased MSI within individual and composite CRC biopsies from LS patients, and within preoperative urine cell free DNA (cfDNA) from two LS patients, one with an upper tract urothelial cancer, the other an undiagnosed endometrial cancer. Approximately 60–70% of the urine cfDNAs were tumour-derived. Our results suggest that mPCR sequence-based analysis of MSI and mutation hotspots in CRC biopsies could facilitate presurgery decision making, and could enable postal-based screening for urinary tract and endometrial tumours in LS patients.

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“…To the best of our knowledge, this study is the first to describe detailed MSI profiles of non‐colorectal gastrointestinal cancers in comparison with those of colorectal cancers. Many previous studies have investigated MSI profiles of colorectal cancers as well as endometrial cancers; however, the number of studies on MSI status of gastric and small intestine cancers is limited 10–13,16 . According to the results of these studies, the concordance rate of MSI status between IHC and MSI testing ranged from 88.8 to 98.8% in gastric cancer, 10–12 whereas in cancers of the small intestine the concordance rate was 100% 16 .…”

Section: Discussionmentioning

confidence: 99%

Microsatellite instability profiles of gastrointestinal cancers: comparison between non‐colorectal and colorectal origin

et al. 2022

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Microsatellite instability profiles of gastrointestinal cancers: comparison between non-colorectal and colorectal originMicrosatellite instability (MSI) is a major carcinogenic pathway with prognostic and predictive implications. The validity of polymerase chain reaction (PCR)-based MSI testing is well established in colorectal cancer; however, the data are limited in non-colorectal gastrointestinal cancers. The aim of this study is to clarify the detailed MSI profiles of non-colorectal gastrointestinal cancers and to investigate the differences from those of colorectal cancers. MSI testing was performed using paired tumour/normal tissues of 123 mismatch repair-deficient cancers detected by immunohistochemistry including 80 non-colorectal cancers (eight oesophagogastric junction (EGJ), 57 gastric and 15 small intestine) and 43 colorectal cancers. Fragment size analysis revealed that the mean nucleotide shifts of five markers (Promega panel) were the highest in the stomach (6.4), followed by colorectum (5.7), small intestine (5.0) and EGJ cancers (mean = 4.0; P = 0.015, versus stomach). All cases showed ≥ 1 nucleotide shift in ≥ 2 markers and were considered as MSI-high. However, when the cut-off was set to ≥ 3 nucleotide shifts in ≥ 2 markers, three EGJ (37.5%), two small intestine (13.3%) and two gastric (3.5%) cancers showed false-negative results. In addition, cases with isolated loss of MSH6 or PMS2 showed smaller nucleotide shifts than those in others. MSI testing is applicable to non-colorectal gastrointestinal cancers; however, a subset can yield false-negative results due to subtle nucleotide shift in multiple markers. Analysis of paired tumour/normal tissues and careful interpretation is necessary to avoid false-negative results and ensure appropriate treatment.

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MSI Analysis in Solid and Liquid Biopsies of Gastroesophageal Adenocarcinoma Patients: A Molecular Approach

Cited by 9 publications

References 32 publications

Microsatellite Instable Colorectal Adenocarcinoma Diagnostics: The Advent of Liquid Biopsy Approaches

Microsatellite Instable Colorectal Adenocarcinoma Diagnostics: The Advent of Liquid Biopsy Approaches

Detection of Microsatellite Instability in Colonoscopic Biopsies and Postal Urine Samples from Lynch Syndrome Cancer Patients Using a Multiplex PCR Assay

Microsatellite instability profiles of gastrointestinal cancers: comparison between non‐colorectal and colorectal origin

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