Capture probes and uses thereof
Inventors
ECCO, Gabriela • XING, Xiaobin • WILLIG, Adrian • XU, Zhenyu
Assignees
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Publication Number
US-12247255-B2
Publication Date
2025-03-11
Expiration Date
Abstract
The present invention is directed to the probes for detecting known and unknown fusion genes, related methods of detection of fusion genes, uses and kits related thereto. In particular, the invention relates to methods of diagnosing and monitoring of a cancer.
Core Innovation
The document describes capture probe designs for fusion gene detection and exon-skipping detection using hybridization capture-based targeted NGS. The probes overlap a breakpoint between a primary nucleotide portion and a secondary nucleotide portion of a target nucleic acid, and at least one probe includes a first portion complementary to the primary nucleotide portion and a second portion complementary to the secondary nucleotide portion.
To reduce capture of unwanted reads from the secondary partner of a fusion or from the wild-type locus, the length of the second portion is limited relative to a total probe length. The second portion represents about 9% to about 42% of the total probe length in the probe set, and in a specific embodiment the second portion is 10 to 50 base pair long with a total probe length of 120 bp.
The document further describes combining universal probes with multiple low-overlap probes having different breakpoint overlap lengths. This mixing captures more fusion fragments than 0 bp probes alone while still reducing background from secondary-partner reads, and the description includes definitions of primary versus secondary fusion partners and breakpoint overlap.
Claims Coverage
The partial content includes two independent claims. Across both, the inventive coverage centers on breakpoint-overlapping probes with a limited-length second portion targeting a primary and a secondary nucleotide portion, with an additional probe complementary only to the primary nucleotide portion in the probe-set claim.
Breakpoint-overlapping probe set with limited second portion and primary-only further probes
A probe set comprising at least one probe having a first portion complementary to a primary nucleotide portion and a second portion complementary to a secondary nucleotide portion, where the probe overlaps a breakpoint between the primary and secondary nucleotide portions, and wherein the length of the second portion represents about 9% to about 42% of a total probe length; and at least one further probe complementary only to the primary nucleotide portion that does not overlap a breakpoint between the primary and secondary nucleotide portion.
Two-part probe overlapping breakpoint with constrained lengths
A probe comprising a first portion complementary to a primary nucleotide portion selected from a fusion gene or transcript encoding a primary fusion partner or an exon skipping transcript encoding one exon, and a second portion complementary to a secondary nucleotide portion selected from a fusion gene or transcript encoding a secondary fusion partner or an exon skipping transcript encoding a secondary exon, where the probe overlaps a breakpoint between the primary and secondary nucleotide portion, and wherein the length of the second portion is 10 to 50 bp long and a total probe length is 120 bp.
Overall, the claims cover capture probes and probe sets that overlap a breakpoint between primary and secondary nucleotide portions while constraining the second portion length. The probe-set claim further requires at least one additional probe that complements only the primary nucleotide portion and does not overlap the breakpoint.
Stated Advantages
Capture of more fusion fragments than 0 bp alone while reducing background from WT secondary partner reads.
Documented Applications
Detection of fusion genes and fusion breakpoints using hybridization capture-based targeted NGS and targeted DNA-seq/RNA-seq in cancer diagnosis and monitoring.
Detection of exon-skipping transcript events using hybridization capture-based targeted NGS and targeted RNA-seq.
Use of the probe sets and probes as part of kits and compositions.
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