Long Read Sequencing for Cancer Research

Cancer is a disease caused primarily by genomic aberrations. Using many rapidly emerging sequencing technologies, researchers have studied cancer genomes to understand the molecular state of cancer cells and reveal their vulnerabilities, such as driver mutations or gene expression. CD Genomics is a leading global life sciences company providing specialized long read sequencing solutions for cancer research. We aim to help our customers identify and characterize novel cancerous mutations, including complex structural variants in haplotype resolution.

Introduction to Cancer

Cancer is an inherited disease caused by changes or mutations in human DNA. These mutations can occur in a variety of ways, some of which affect the function of driver and oncogenes, leading to abnormal proliferation as well as the initiation or progression of cancer. DNA sequencing is an important tool in the diagnosis and treatment of cancer because it provides a snapshot of these mutations. Scientists have long used primarily short-read genome sequencing to explore the mutational landscape of cancer. Short-read genome sequencing technology is high-throughput but only generates many short DNA fragments, which researchers then piece together to identify mutations in the genome using computational tools. However, it remains difficult to detect more complex or larger-scale structural aberrations, such as chromosomal aneuploidies, copy number aberrations, and rearrangements, based only on short-read long sequencing data. Scientists are seeking better ways to analyze the effects of somatic structural variants (SSVs) on cellular function. These SSVs are rearrangements of large DNA fragments (e.g., deletions, duplications, etc.), and they are known to be associated with most oncogenic mutations.

Fig. 1. Structural variants in lung cancers identified by PromethION. (Sakamoto et al., 2020)

Solutions Offering at CD Genomics

Based on our advanced PacBio SMRT sequencing and ONT Nanopore sequencing platforms, our lon read sequencing solutions are tailored for cancer research and help detect previously overlooked or undetectable mutations.

Our long read sequencing provides reliable detection of cancer mutations. Our long read sequencing services for cancer research are included below:

• Long Read Sequencing of Cancer Genomes

Cancer genomes are notorious for their complex mutations, many of which are buried deep within regions of the genome that are traditionally elusive to short read long sequencing. Long read sequencing, with its ability to read extended-length DNA, provides a way to elucidate complex structural variants, repetitive sequences, and even haplotype stereotypes. Through powerful sampling and analysis, our long read sequencing allows for detecting and understanding of complex genomic rearrangements and structural variants in cancer. This is particularly useful in cancer genomics, especially for sarcomas, esophageal and ovarian cancers.

• Full-length Transcriptome of Cancer Cells

Long reads are able to completely cover full-length transcript sequences, so the structure of transcript isoforms can be determined by sequencing full-length complementary DNA (cDNA). We offer long read sequencing to detect splice isoforms and fusion transcripts, which are major driver events in carcinogenesis in several types of cancer (e.g., lung adenocarcinoma).

• We use PacBio SMRT sequencing for full-length cDNA sequencing, which permits the detection of fusion transcripts in addition to genomic aberrations in breast cancer.
• We offer nanopore sequencing for full-length transcript sequencing of lung cancer cell lines, allowing rapid detection of multiple heterozygous mutations, including SNVs (e.g., EGFR mutations) associated with sensitivity to molecularly targeted drugs, which can be sequenced and phased.
• N6-methyladenine (m6A) is implicated in the survival and maintenance of multiple cancer types, such as myeloid leukemia and lung cancer. We provide full-length modified pairs of RNA for analysis to identify unknown features and novel therapeutic targets in cancer cells.

• Long Read Sequencing of Cancer Epigenomics

DNA modifications play an important role in various biological events through transcriptional regulation. In cancer cells, we frequently observe genome-wide hypomethylation leading to chromosomal instability. In addition, hypermethylation occurs particularly in the CpG islands of tumor suppressor gene promoters, leading to silencing of genes such as cell cycle regulators and mismatch repair factors. We use PacBio sequencing to develop long read bisulfite protocols that allow the analysis of methylation in blood malignant cell lines in a single continuous molecule. In addition, we offer nanopore sequencing to directly detect methylated DNA in cancer.

Advantages of Our Long Read Sequencing Solutions for Cancer Research

• Highly accurate sequencing allows you to discover new isoforms, fusions, and structural variants with extreme accuracy.
• Easier identification and characterization of mutations in each cancer.
• Ideal for elucidating allele-resolution mutation states and the complete structure of complex cancer genomes.
• Characterizes genomic mutations at single allele resolution.
• Helping researchers and clinicians can lead to more targeted and effective treatment strategies.

CD Genomics is committed to providing accurate, comprehensive, and high-resolution long read sequencing solutions to accelerate cancer research. Our goal is to identify key driver mutations and tumor suppressor aberrations that pave the way for targeted therapeutic interventions. If you have any questions, please feel free to contact us. We look forward to working with you on projects of interest.

Related Services

PacBio SMRT Sequencing
Oxford Nanopore Sequencing
Long-Read Sequencing of DNA Methylation
Long-Read Sequencing of RNA Methylation
Full-Length Transcript Sequencing (Iso-Seq)
Nanopore Full-Length cDNA Sequencing