Molecular Analysis of Iranian Colorectal Cancer Patients at Risk for Lynch Syndrome: a New Molecular, Clinicopathological Feature

Zeinalian, Mehrdad; Salehi, Roya; Naimi, Azar; Kazemi, Mohammad; Chaleshtori, Morteza Hashemzadeh

doi:10.1007/s12029-015-9696-1

Cited by 11 publications

(13 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6,15 The 5 markers were also used in our center, and it is of note that both BAT25 and BAT26 were unstable in all MSI-H tumors in our present cohort, similar to the previous studies. [7][8][9] Therefore, care should be taken before scoring a MSI-H tumor with stable BAT25 or BAT26; samples mix-up must be first excluded. Given the high frequency of BAT26-unstable tumors, one study suggested that BAT26 may be used for the initial MSI screening in sporadic CRCs in regions with limited resources.…”

Section: Discussionmentioning

confidence: 99%

Increasing Demand for MSI Testing and Prevalence of MSI-H Cancers in Thai Patients: Experience at Chulalongkorn GenePRO Center.

Laohawetwanit¹,

Boonkasem²,

Thongsawang³

et al. 2019

bkkmedj

View full text Add to dashboard Cite

NA mismatch repair (MMR) is necessary for all organisms in order to maintain DNA integrity. Loss of expression of one of the MMR proteins results in several sporadic and inherited human cancers of various organs such as colon, rectum, stomach, uterus, and ovary. 1 Microsatellite instability (MSI) was shown to be associated with some cancer types, better survival and/or outcome, and reduced likelihood of distant metastases and susceptible to chemotherapy. 2-4 Either immunohistochemical study showing loss of MMR proteins expression or PCR-based assay for microsatellite instability can be used to evaluate the MMR status of cancer tissue. 5 Colorectal cancer (CRC), particularly those occurring in the setting of Lynch syndrome, is the prototype of malignancy with microsatellite instability. MMR status has extensively been studied in CRCs 3,4,6-10 and although deficiency of DNA mismatch repair was reported in 15% of Thai patients with sporadic CRCs, 11 MSI testing is not routinely performed as part of the clinical practice in Thailand. Immunotherapy has played a significant role in cancer treatment and recent clinical studies have suggested that mismatch repair-deficient cancers, regardless of tissue origin, are susceptible to immune-checkpoint inhibitors e.g. PD-1 blockade. 12,13 In May 2017, the US Food and Drug Administration (FDA) granted an accelerated approval to pembrolizumab, an antibody to the PD-1 receptor, as an alternative Abstract RATIONALE: Loss of DNA mismatch repair function has long been known in various malignancies, particularly colorectal cancer. However, microsatellite instability (MSI) testing was rarely requested in Thailand. Recently, the US Food and Drug Administration (FDA) has approved pembrolizumab, an antibody to PD-1 receptor, as an alternative treatment for high MSI (MSI-H) and/or MMR (mismatch repair)-deficient solid tumors. We report our recent observation on MSI testing in Thailand. MATERIALS AND METHODS: Data was collected from Chulalongkorn GenePRO Center, Faculty of Medicine, Chulalongkorn University, during July 2013 and July 2017. MSI testing was performed, using 5 microsatellite markers (BAT-25, BAT-26, D2S123, D5S346 and D17S250). The number, source, and result of samples underwent MSI assay were analyzed. RESULTS: Requests for MSI testing have increased significantly in recent years. The shift started in 2015 when the MMR status was found to predict clinical benefit with the immune checkpoint blockade. There were 118 (75.2%) colorectal, 11 (7%) gastric, and 28 (17.8%) other cancers tested. MSI-H, MSI-L, and microsatellite stable (MSS) tumors were detected in 18 (11.5%), 11 (7%), and 128 (81.5%) patients, respectively. Of the 18 MSI-H cancers; 13 (72.2%), 4 (22.2%), and 1 (5.6%) were colorectal, gastric, and gynecologic malignancy, respectively. BAT25 and BAT26 markers were unstable in all MSI-H tumors. CONCLUSION: We have experienced increasing demand for MSI testing in Thai patients at Chulalongkorn GenePRO Center. Colorectal cancers were most frequently tested, and accounted ...

show abstract

Section: Discussionmentioning

confidence: 99%

Increasing Demand for MSI Testing and Prevalence of MSI-H Cancers in Thai Patients: Experience at Chulalongkorn GenePRO Center.

Laohawetwanit¹,

Boonkasem²,

Thongsawang³

et al. 2019

bkkmedj

View full text Add to dashboard Cite

show abstract

“…Overall, there are at least three main molecular pathways underlying the development of colorectal cancer (CRC): Chromosomal instability (CIN) pathway, microsatellite instability (MSI) pathway, and CpG island methylator phenotype (CIMP) pathway. [ 1 2 3 ] CIN is the most prevalent molecular cause of genomic instability in CRC, so it is an original genetic basis of about 65%–70% of all sporadic CRC tumors. [ 4 ] CIN is characterized with an imbalance in number of chromosomes (aneuploidy), chromosomal amplification, and a high frequency of loss of heterozygosity resulting in some deleterious mutations in tumor suppressor genes such as APC and TP53 , and oncogenes including KRAS .…”

Section: What Are Molecular Pathways Behind Colorectal Cancer?mentioning

confidence: 99%

“…MSI is a particular molecular change as a hallmark of averagely 15% of CRCs. [ 3 9 ] At first, these molecular changes were named “dispersed somatic mutations” in simple tandem repeats[ 13 ] or a replication error phenotype (RER). [ 14 ] Due to a defect in DNA-mismatch repair (MMR) system, microsatellites or short tandem repeats, repetitive sequences containing 1–6 nucleotide units up to 100 times, are prone to accumulation of mutations.…”

Section: What Is Microsatellite Instability?mentioning

confidence: 99%

Clinical Aspects of Microsatellite Instability Testing in Colorectal Cancer

Zeinalian

Hashemzadeh‐Chaleshtori

Salehi

2018

Adv Biomed Res

Self Cite

View full text Add to dashboard Cite

Microsatellite instability (MSI) is a molecular hallmark for some colorectal cancers (CRCs) in which short tandem repeats are prone to mutations along with DNA sequences. It is due to DNA-mismatch-repair system deficiency because of a germline/somatic mutation in mismatch-repair (MMR) genes. The germline mutations lead to Lynch syndrome (LS) while epigenetic gene silencing results in sporadic CRC tumors. We discuss in our paper the most important clinical aspects of MSI testing in CRCs. We reviewed the most reliable relevant studies and clinical trials according to their high-quality methods, particularly within two recent decades. MSI testing is used to classify CRC tumors as MSI-high (MSI-H), MSI-low, and microsatellite stable tumors. MSI-H or MMR deficient tumors have shown the best prognosis among all CRCs, so MSI testing is considered as a good prognostic marker. Moreover, it is used to identify LS among familial CRC patients. There is a diagnostic mutation in BRAF gene (V600E) by which sporadic CRCs could be distinguished from LS associated CRCs, due to its concordance with sporadic CRCs not LS. Although, some previous studies had demonstrated a predictive role for MSI testing in chemotherapy process, emerging some controversial findings in recent studies has not convinced many authors to recommend it as a routine examination to evaluate therapeutic response. Though emerging new molecular findings have opened novel windows to develop clinical management of CRC, MSI testing has remained as an excellent prognostic and diagnostic tool for CRC tumors.

show abstract

“…The basic tests identify five markers (NR-21, BAT-26, BA T -25, NR-27 and NR-24) to devise the simplest diagnostic assay (9). Previous reports have shown significant diversity regarding the most common marker for microsatellite testing; BAT 25, BAT26 and NR21 have been reported in HNPCC and sporadic CRCs (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Table 1 shows the reports from Iran that studied the frequency of MMR genes in both hereditary and sporadic colorectal cancers.…”

Section: Microsatellite Instability (Msi)mentioning

confidence: 99%

“…Table 1 shows the reports from Iran that studied the frequency of MMR genes in both hereditary and sporadic colorectal cancers. As it shows, the frequency of MSI in patients with HNPCC has been 29% -62.5% (9-25), there are not so many studies about the frequency of MSI in sporadic CRC from Iran; however, the reported frequencies of MMR have been from 19.4% to 66.6% (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

Section: Microsatellite Instability (Msi)mentioning

confidence: 99%

Molecular Biomarkers of Colorectal Cancer: A Review of Published Articles From Iran

Geramizadeh

2015

Ann Colorectal Res

View full text Add to dashboard Cite

Context: Colorectal cancer is one of the most common cancers worldwide (the third most common cancer in the world) and is especially more common in Western countries; however, its incidence has been increased significantly during the last few years in Eastern countries such as Iran and considered as one of the five common cancers in this country. According to molecular pathways, numerous biomarkers have been identified for colorectal cancers which help patients' management. Evidence aquisition: In this study, we tried to review published articles about the molecular biomarkers of colorectal cancer from Iran. We searched medical databases such as google scholar, Scopus, PubMed, Magiran, SID and Iran Medex for keywords of "colon cancer, KRAS, BRAF, mismatch repair gene, Microsatellite instability, molecular genetics, molecular pathogenesis, biomarker and Iran" to find studies published about colorectal cancers from Iran regarding molecular biomarkers. Conclusion: This study showed that molecular biomarkers in colorectal cancer of Iranian patients are not so different from Western population.

show abstract

Molecular Analysis of Iranian Colorectal Cancer Patients at Risk for Lynch Syndrome: a New Molecular, Clinicopathological Feature

Abstract: A different molecular and clinicopathological phenotype of tumors in CRC Iranian patients at risk for Lynch syndrome could suggest some new molecular mechanisms about which more evaluations are necessary.

Cited by 11 publications

References 40 publications

Increasing Demand for MSI Testing and Prevalence of MSI-H Cancers in Thai Patients: Experience at Chulalongkorn GenePRO Center.

Increasing Demand for MSI Testing and Prevalence of MSI-H Cancers in Thai Patients: Experience at Chulalongkorn GenePRO Center.

Clinical Aspects of Microsatellite Instability Testing in Colorectal Cancer

Molecular Biomarkers of Colorectal Cancer: A Review of Published Articles From Iran

Contact Info

Product

Resources

About