Publications by authors named "Siew-Kee Low"

Article Synopsis
  • * A 70-year-old woman with a history of PBM was diagnosed with PVca after endoscopy showed a tumor, and subsequent surgery revealed specific carcinogenic changes consistent with the hyperplasia-dysplasia-carcinoma sequence.
  • * The study concludes that this case marks the first documentation of PVca related to PBM using advanced techniques like immunostaining and next-generation sequencing, highlighting the need for ongoing monitoring in similar patients.
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Background: KRAS mutation positive lung cancer is known to be clinically characterized by older age, males, and smokers. It is reported to be more common in mucinous adenocarcinoma, but all reports are based on analysis of tissue samples. Recently, blood samples have become available for analysis, suggesting a low detection rate of circulating tumor DNA in histological types, especially mucinous adenocarcinoma.

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Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis.

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Introduction: Circulating tumor DNA (ctDNA) has been increasingly recognized as a promising minimally-invasive biomarker that could identify patients with minimal residual disease and a high risk of recurrence after definitive treatment. In this study, we've compared the clinical utility and sensitivity of 2 different approaches to ctDNA analyses: tumor-informed and tumor-agnostic in the management of colorectal (CRC) patients. The clinical benefits of a single timepoint ctDNA analysis compared to serial ctDNA monitoring after definitive treatment were also evaluated to uncover the ideal surveillance protocol.

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  • Epilepsy is influenced by both genetic and environmental factors, with recent studies focusing on genetic risk variants and how they affect the balance between excitation and inhibition in the brain.
  • Researchers identified two specific genetic variants (GABRA1 and ERBB4) in a Malaysian Chinese family affected by genetic generalized epilepsy, which were linked to disturbances in this balance.
  • While all affected family members had both variants, those with only one variant showed no symptoms, indicating that the combination of both variants may lead to a greater risk of seizures and reinforcing the need for more research to confirm these findings.
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  • - The study analyzed data from over 160,000 breast cancer patients and 226,000 controls from Asian and European backgrounds to explore genetic factors linked to breast cancer risk, identifying 222 genetic risk loci and 137 associated genes.
  • - Among these, 32 loci and 15 genes showed varying levels of association between estrogen receptor (ER)-positive and ER-negative breast cancer after accounting for statistical correction.
  • - The research also revealed significant differences based on ancestry in risk allele frequencies and highlighted new potential genetic variants not previously associated with breast cancer, contributing to a broader understanding of the disease's genetic landscape.
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Pancreatic cancer is one of the cancers with very poor prognosis; there is an urgent need to identify novel biomarkers to improve its clinical outcomes. Circulating tumor DNA (ctDNA) from liquid biopsy has arisen as a promising biomarker for cancer detection and surveillance. However, it is known that the ctDNA detection rate in resected pancreatic cancer is low compared with other types of cancer.

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The rearrangement of anaplastic lymphoma kinase (ALK) occurs in 3%-5% of patients with non-small cell lung cancer (NSCLC) and confers sensitivity to ALK-tyrosine kinase inhibitors (TKIs). For the treatment of patients with ALK-rearranged NSCLC, various additional ALK-TKIs have been developed. Ceritinib is a second-generation ALK-TKI and has shown great efficacy in the treatment of patients with both newly diagnosed and crizotinib (a first-generation ALK-TKI)-refractory ALK-rearranged NSCLC.

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Genomic profiling using tumor biopsies remains the standard approach for the selection of approved molecular targeted therapies. However, this is often limited by its invasiveness, feasibility, and poor sample quality. Liquid biopsies provide a less invasive approach while capturing a contemporaneous and comprehensive tumor genomic profile.

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Neuroendocrine carcinomas (NECs), a poorly differentiated subtype of neuroendocrine neoplasms, are aggressive and have a poor prognosis. Colorectal neuroendocrine carcinomas (CRC-NECs) are observed in about 0.6% of all patients with CRC.

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Background: Genomic profiling of tumors from cancer patients facilitates molecular-guided therapy. The turnaround time is one of important issues to deliver results timely for clinical decisions. The Ion Torrent™ Genexus™ Integrated Sequencer automates all next generation sequencing (NGS) workflows and delivers results within a day.

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In the field of colorectal cancer (CRC) treatment, diagnostic modalities and chemotherapy regimens have progressed remarkably in the last two decades. However, it is still difficult to identify minimal residual disease (MRD) necessary for early detection of recurrence/relapse of tumors and to select and provide appropriate drugs timely before a tumor becomes multi-drug-resistant and more aggressive. We consider the leveraging of in-depth genomic profiles of tumors as a significant breakthrough to further improve the overall prognosis of CRC patients.

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Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancer types. Activating oncogenic mutations are commonly observed in PDAC; however, oncogenic amplification is rarely observed, and its significance in prognosis and resistance to therapy remains poorly characterized. The present report describes the case of a 52-year-old male patient diagnosed with advanced PDAC with liver metastasis.

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There are numerous histological subtypes (histotypes) of gynecological malignancies, with each histotype considered to largely reflect a feature of the "cell of origin," and to be tightly linked with the clinical behavior and biological phenotype of the tumor. The recent advances in massive parallel sequencing technologies have provided a more complete picture of the range of the genomic alterations that can persist within individual tumors, and have highlighted the types and frequencies of driver-gene mutations and molecular subtypes often associated with these histotypes. Several large-scale genomic cohorts, including the Cancer Genome Atlas (TCGA), have been used to characterize the genomic features of a range of gynecological malignancies, including high-grade serous ovarian carcinoma, uterine corpus endometrial carcinoma, uterine cervical carcinoma, and uterine carcinosarcoma.

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Liquid biopsies have been receiving tremendous attentions as easy, rapid, and non-invasive tools for cancer diagnosis. Liquid biopsy can be performed repeatedly for disease monitoring and is expected to overcome the limitations of tissue biopsies. With the advancement of next generation sequencing technologies, it is now possible to detect minute amount of tumor-derived circulation tumor DNA (ctDNA) from blood samples.

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Introduction: CYP2D6 protein activity can be inferred from the ratio of N-desmethyl-tamoxifen (NDMT) to endoxifen (E). CYP2D6 polymorphisms are common and can affect CYP2D6 protein activity and E level. Some retrospective studies indicate that E < 16 nM may relate to worse outcome.

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We present a study to evaluate the feasibility and clinical utility of amplicon-based Oncomine Pan-Cancer cell-free assay to detect circulating tumor DNA (ctDNA) in patients with early or advanced breast cancer. In this study, 109 early and metastatic breast cancer patients were recruited before the initiation of treatment. ctDNA mutation profiles were assessed through unique molecular tagging (UMT) and ultradeep next generation sequencing (NGS).

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The use of blood liquid biopsy is being gradually incorporated into the clinical setting of cancer management. The minimally invasive nature of the usage of cell-free DNA (cfDNA) and its ability to capture the molecular alterations of tumors are great advantages for their clinical applications. However, somatic mosaicism in plasma remains an immense challenge for accurate interpretation of liquid biopsy results.

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Cancer pharmacogenomics is the science concerned with understanding genetic alterations and its effects on the pharmacokinetics and pharmacodynamics of anti-cancer drugs, with the aim to provide cancer patients with the precise medication that will achieve a good response and cause low/no incidence of adverse events. Advances in biotechnology and bioinformatics have enabled genomic research to evolve from the evaluation of alterations at the single-gene level to studies on the whole-genome scale using large-scale genotyping and next generation sequencing techniques. International collaborative efforts have resulted in the construction of databases to curate the identified genetic alterations that are clinically significant, and these are currently utilized in clinical sequencing and liquid biopsy screening/monitoring.

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Article Synopsis
  • Blood-based analysis of circulating tumor DNA (ctDNA) is an effective method for cancer-related monitoring, but there's a need to compare serum and plasma samples to understand their efficiency as ctDNA sources.
  • In a study comparing matched serum and plasma samples from cancer patients and healthy donors, it was found that serum had higher total cell-free DNA (cfDNA) but lower mutation detection sensitivity, particularly for low allele frequencies.
  • The results suggest that while serum samples can be used for certain retrospective studies, plasma is recommended for future clinical applications due to better mutation detection rates.
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The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P < 9.

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  • * Researchers examined plasma cfDNA and matched tumor tissues from 38 patients, identifying a total of 74 mutations in tumor tissues and 64 in plasma, with some mutations linked to clonal hematopoiesis (CH).
  • * The presence of CH-related mutations in plasma cfDNA highlighted the need to differentiate these from tumor-derived mutations, as misinterpretation could lead to incorrect conclusions about cancer treatment effectiveness and residual disease.
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Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10.

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