Methods For Early Detection Of Cancer

What is this patent about?

’640 is related to the field of early cancer detection using next-generation sequencing (NGS) of cell-free DNA (cfDNA). The background context is the need for more sensitive and specific methods to detect cancer, especially in early stages or after treatment, where circulating tumor DNA (ctDNA) levels may be very low. Existing methods often lack the sensitivity to detect these low levels, leading to delayed diagnoses or incomplete assessment of treatment efficacy.

The underlying idea behind ’640 is to use a targeted sequencing approach on cfDNA to identify tumor-specific markers, such as genetic variants and methylation patterns, with high sensitivity and specificity. The key inventive insight is to combine sequence capture of a panel of genes or genomic regions known to be associated with cancer, with deep sequencing and analysis of methylation profiles, to detect residual disease after treatment.

The claims of ’640 focus on a method for detecting the presence or absence of residual disease in a subject. This involves enriching cfDNA molecules using sequence capture for a sequencing panel of genes or genomic regions. The sequencing panel is at least 150kb, includes genes or genomic regions with differentially methylated CpG islands, and genes or genomic regions associated with one or more cancers. The method further involves sequencing the enriched cfDNA and determining methylation profiles and detecting genetic variants to detect residual disease.

In practice, the method involves obtaining a blood sample from a subject who has previously received cancer treatment. The cfDNA is extracted and then enriched using sequence capture with probes designed to target the specified panel of genes and genomic regions. The enriched cfDNA is then sequenced using NGS to generate a large number of reads. The resulting sequencing data is analyzed to identify both genetic variants (SNVs, indels, etc.) and methylation patterns that are indicative of residual disease.

This approach differentiates itself from prior methods by combining a relatively large sequencing panel (at least 150kb) with the analysis of both genetic variants and methylation profiles. Prior approaches may have focused on smaller panels or only on genetic variants, potentially missing important information about tumor heterogeneity and epigenetic changes. By targeting differentially methylated regions, the method can potentially identify tumor-specific signals even when genetic variants are rare or absent, improving sensitivity and specificity for detecting residual disease.