Cancers, Vol. 15, Pages 4245: Immunotherapy for Colorectal Cancer with High Microsatellite Instability: The Ongoing Search for Biomarkers
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Microsatellite instability (MSI) is a biological condition associated with inflamed tumors, high tumor mutational burden (TMB), and responses to immune checkpoint inhibitors. In colorectal cancer (CRC), MSI tumors are found in 5% of patients in the metastatic setting and 15% in early-stage disease. Following the impressive clinical activity of immune checkpoint inhibitors in the metastatic setting, associated with deep and long-lasting responses, the development of immune checkpoint inhibitors has expanded to early-stage disease. Several phase II trials have demonstrated a high rate of pathological compl...
Source: Cancers - August 24, 2023 Category: Cancer & Oncology Authors: Ros Baraibar Saoudi Rodriguez Salv à Tabernero Élez Tags: Review Source Type: research
Lynch syndrome-associated upper tract urothelial carcinoma frequently occurs in patients older than 60 years: an opportunity to revisit urology clinical guidelines
In this study, we examined a cohort of patients with UTUC for potential association with LS in order to establish the sensitivity of current guidelines in detecting LS. A total of 180 patients with confirmed diagnosis of UTUC were enrolled in the study during a 12-year period (2010–2022). Loss of DNA-mismatch repair proteins (MMRp) expression was identified in 15/180 patients (8.3%). Germline analysis was eventually performed in 8 patients confirming LS in 5 patients (2.8%), including 4 germline mutations inMSH6 and 1 germline mutation inMSH2. LS-related UTUC included 3 females and 2 males, with a mean age of 66.2 year...
Source: Virchows Archiv - August 23, 2023 Category: Pathology Source Type: research
Constitutional mismatch repair deficiency syndrome with atypical features caused by a homozygous MLH1 missense variant (c.1918C > A, p.(Pro640Thr)): a case report
We report a homozygous MLH1 missense variant (c.1918C>A p.(Pro640Thr)) in a Tunisian patient with CMMRD syndrome and a family history of early-age colorectal cancer. The proband presented initially with colonic oligopolyposis and adenosquamous carcinoma of the caecum. He later developed several malignancies, including undifferentiated carcinoma of the parotid, grade 4 IDH-mutant astrocytoma, and ampulla of Vater adenocarcinoma. The patient was older than typical for this disease and had a remarkably prolonged survival despite developing four distinct aggressive malignancies. The current report highlights the challenges ...
Source: Frontiers in Oncology - August 17, 2023 Category: Cancer & Oncology Source Type: research
Cancers, Vol. 15, Pages 4074: Variant Characterization of a Representative Large Pedigree Suggests & ldquo;Variant Risk Clusters & rdquo; Convey Varying Predisposition of Risk to Lynch Syndrome
In this study, we seek novel familial germline variants from a large pedigree Tunisian family with 12 LS-affected individuals to identify putative germline variants associated with varying risk of LS. Whole-genome sequencing analysis was performed to identify known and novel germline variants shared between affected and non-affected pedigree members. SNPs, indels, and structural variants (SVs) were computationally identified, and their oncological influence was predicted using the Genetic Association of Complex Diseases and Disorders, OncoKB, and My Cancer Genome databases. Of 94 germline familial variants identified with ...
Source: Cancers - August 12, 2023 Category: Cancer & Oncology Authors: Mouadh Barbirou Amanda A. Miller Amel Mezlini Balkiss Bouhaouala-Zahar Peter J. Tonellato Tags: Article Source Type: research
PREMM5 distinguishes sporadic from Lynch syndrome-associated MMR-deficient/MSI-high colorectal cancer
AbstractCurrent algorithms for diagnosing Lynch syndrome (LS) include multistep molecular tumor tests to distinguish LS-associated from sporadic colorectal cancer (CRC), which add cost and complexity to the evaluation. We hypothesized that PREMM5, a clinical LS prediction tool, could be an alternative approach to screen for LS, thereby lessening the need for specialized molecular diagnostics. We reviewed a consecutively ascertained institutional cohort of 1058 CRC patients on whom pathologic and clinical data were available, including prior LS germline testing. Data from MMR-D/MSI-H CRC patients were reviewed and PREMM5 sc...
Source: Familial Cancer - August 12, 2023 Category: Cancer & Oncology Source Type: research
Immune microenvironment profiling of normal appearing colorectal mucosa biopsied over repeat patient visits reproducibly separates lynch syndrome patients based on their history of colon cancer
DiscussionThis prospective pilot study demonstrated that immune profiling of normal appearing colonic mucosa discriminates LS patients with a prior history of CRC from those without it, as well as patients with a history of sporadic CRC from HC. Importantly, it suggests the existence of immune signatures specific to LS-status and CRC history. We anticipate that our findings have the potential to assess CRC risk in individuals with LS and help in preemptively mitigating it by optimizing surveillance and identifying candidate prevention targets. Further studies are required to validate our findings in an independent cohort o...
Source: Frontiers in Oncology - August 11, 2023 Category: Cancer & Oncology Source Type: research
Treatment of Microsatellite-Unstable Rectal Cancer in Sporadic and Hereditary Settings
Clin Colon Rectal Surg DOI: 10.1055/s-0043-1770717Microsatellite instability is rare in rectal cancer and associated with younger age of onset and Lynch syndrome. All rectal cancers should be tested for microsatellite instability prior to treatment decisions. Patients with microsatellite instability are relatively resistant to chemotherapy. However, recent small studies have shown dramatic response with neoadjuvant immunotherapy. Patients with Lynch syndrome have a hereditary predisposition to cancer and thus an elevated risk of metachronous cancer. Therefore, while “watch and wait” is a well-established practice for s...
Source: Clinics in Colon and Rectal Surgery - August 11, 2023 Category: Surgery Authors: Anderson, Cristan E. Liska, David Tags: Review Article Source Type: research
Management of Rectal Cancer in Lynch Syndrome: Balancing Risk Reduction and Quality of Life
Clin Colon Rectal Surg DOI: 10.1055/s-0043-1770730Patients with Lynch syndrome are predisposed to developing colorectal cancer and a variety of extracolonic malignancies, at a young age. The management of rectal cancer in the setting of Lynch syndrome is a complex clinical scenario that requires the expertise of a multidisciplinary management team. In this review, we delve into the approach for rectal cancer in these patients, and specifically focus on several key aspects of treatment. Some unique aspects of rectal cancer in Lynch syndrome include the decision between proctectomy alone versus total proctocolectomy with or ...
Source: Clinics in Colon and Rectal Surgery - August 10, 2023 Category: Surgery Authors: Krasnick, Bradley A. Kalady, Matthew F. Tags: Review Article Source Type: research
Surveillance of the small-bowel by capsule endoscopy in Lynch syndrome – A systematic review with meta-analysis
The role of small-bowel (SB) cancer surveillance by capsule endoscopy (CE) in Lynch syndrome (LS) patients has been investigated in recent years, with contradicting results. This meta-analysis evaluates the diagnostic yield (DY) of CE as a screening tool in asymptomatic LS patients. (Source: Digestive and Liver Disease)
Source: Digestive and Liver Disease - August 8, 2023 Category: Gastroenterology Authors: Pablo Cortegoso Valdivia, Ulrik Deding, Thomas Bj ørsum-Meyer, Marco Pennazio, Federica Gaiani, Anastasios Koulaouzidis, Luigi Laghi Tags: Meta-Analysis Source Type: research
A Highly Sensitive Pan-Cancer Test for Microsatellite Instability
Microsatellite instability (MSI) is an evolving biomarker for cancer detection and treatment. MSI was first used to identify patients with Lynch syndrome, a hereditary form of colorectal cancer (CRC), but has recently become indispensable in predicting patient response to immunotherapy. To address the need for pan-cancer MSI detection, a new multiplex assay was developed that utilizes novel long mononucleotide repeat markers (LMR) to improve sensitivity. 469 tumor samples from 20 different cancer types, including 319 from patients with Lynch syndrome, were tested for MSI using the new LMR MSI Analysis System. (Source: Jour...
Source: Journal of Molecular Diagnostics - August 4, 2023 Category: Pathology Authors: Jeffery W. Bacher, Eshwar B. Udho, Ethan E. Strauss, Irina Vyazunova, Steven Gallinger, Daniel D. Buchanan, Rish K. Pai, Allyson S. Templeton, Douglas R. Storts, James R. Eshleman, Richard B. Halberg Tags: Regular Article Source Type: research
Genes, Vol. 14, Pages 1580: Co-Occurrence of Germline Genomic Variants and Copy Number Variations in Hereditary Breast and Colorectal Cancer Patients
na Rogatto
Hereditary Breast and Ovarian Cancer (HBOC) syndrome is an autosomal dominant disease associated with a high risk of developing breast, ovarian, and other malignancies. Lynch syndrome is caused by mutations in mismatch repair genes predisposing to colorectal and endometrial cancers, among others. A rare phenotype overlapping hereditary colorectal and breast cancer syndromes is poorly characterized. Three breast and colorectal cancer unrelated patients fulfilling clinical criteria for HBOC were tested by whole exome sequencing. A family history of colorectal cancer was reported in two patients (cases 2 and 3)...
Source: Genes - August 3, 2023 Category: Genetics & Stem Cells Authors: Luiza C ôrtes Tatiane Ramos Basso Rolando Andr é Rios Villacis Jeferson dos Santos Souza Mads Malik Aagaard J ørgensen Maria Isabel Achatz Silvia Regina Rogatto Tags: Article Source Type: research
Cancers, Vol. 15, Pages 3930: Lynch Syndrome Biopathology and Treatment: The Potential Role of microRNAs in Clinical Practice
ndro Tagliaferri
Lynch syndrome (LS), also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is an autosomal dominant cancer syndrome which causes about 2–3% of cases of colorectal carcinoma. The development of LS is due to the genetic and epigenetic inactivation of genes involved in the DNA mismatch repair (MMR) system, causing an epiphenomenon known as microsatellite instability (MSI). Despite the fact that the genetics of the vast majority of MSI-positive (MSI+) cancers can be explained, the etiology of this specific subset is still poorly understood. As a possible new mechanism, it has been...
Source: Cancers - August 2, 2023 Category: Cancer & Oncology Authors: Serena Ascrizzi Grazia Maria Arillotta Katia Grillone Giulio Carid à Stefania Signorelli Asad Ali Caterina Romeo Pierfrancesco Tassone Pierosandro Tagliaferri Tags: Review Source Type: research
Current Trends in Vaccine Development for Hereditary Colorectal Cancer Syndromes
Clin Colon Rectal Surg DOI: 10.1055/s-0043-1770383The coming of age for cancer treatment has experienced exponential growth in the last decade with the addition of immunotherapy as the fourth pillar to the fundamentals of cancer treatment—chemotherapy, surgery, and radiation—taking oncology to an astounding new frontier. In this time, rapid developments in computational biology coupled with immunology have led to the exploration of priming the host immune system through vaccination to prevent and treat certain subsets of cancer such as melanoma and hereditary colorectal cancer. By targeting the immune system through tu...
Source: Clinics in Colon and Rectal Surgery - July 31, 2023 Category: Surgery Authors: Bowen, Charles M. Sinha, Krishna M. Vilar, Eduardo Tags: Review Article Source Type: research
Prevalence and genetic spectrum associated with hereditary colorectal cancer syndromes, the need to improve cancer risk awareness, and family cascade testing in Vietnam
This study aims to define the mutation spectrum associated with hereditary colorectal cancer syndromes (HCCS) in Vietnam, evaluate the influence of genetic testing on carriers’ awareness, and also investigate the barriers in familial testing. Genetic te st reports were collected to identify HCCS cases, then cases underwent a survey investigating self-risk and familial-risk awareness, proactive cancer screening, and familial testing barriers. Participant characteristics, mutation prevalence, and results from the survey were descriptively analyzed an d reported. Of all genetic test results, 3% (49/1632) were identified wit...
Source: Familial Cancer - July 30, 2023 Category: Cancer & Oncology Source Type: research
Familial intestinal polyposis and device assisted enteroscopy: where do we stand?
Expert Rev Gastroenterol Hepatol. 2023 Jul 29:1-6. doi: 10.1080/17474124.2023.2242240. Online ahead of print.ABSTRACTINTRODUCTION: Hereditary polyposis syndromes are a group of inherited disorders associated with a high risk of developing colorectal cancer. The best known ones are familial adenomatous polyposis (FAP), Peutz-Jeghers (PJS), juvenile polyposis and Cowden syndromes, as well as conditions predisposing to cancer, such as Lynch syndrome. Some of them are characterized by an increased risk of small bowel polyps occurrence.AREAS COVERED: Literature search in PubMed was performed in November 2022 and a narrative rev...
Source: Expert Review of Gastroenterology and Hepatology - July 29, 2023 Category: Gastroenterology Authors: Giuseppe Losurdo Milena Di Leo Salvatore Rizzi Ilaria Lacavalla Francesca Celiberto Andrea Iannone Maria Rendina Enzo Ierardi Giuseppe Iabichino Luca De Luca Alfredo Di Leo Source Type: research
