Retrotransposon biomarkers
AssigneesVib Vzw, Katholieke Universiteit Leuven, K.U.Leuven R&D
InventorsDiether Lambrechts, Jieyi Xiong
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Abstract
The invention relates to methods of tumor analysis relying on the detection of expression of or of changes in the expression levels of specific retrotransposons. Such methods find application in, amongst other, predicting the response of a tumor to immunotherapy or to immunogenic therapy, and in following up such responses. The expression levels of specific retrotransposons can thus be used in determining which patients are most likely to respond to immunotherapy or immunogenic therapy. Corresponding diagnostic kits are likewise part of the invention.
Claims22
A method of detecting susceptibility to immunotherapy or immunogenic therapy of a tumor in a subject prior to or early after start of the immunotherapy or of the immunogenic therapy, the method comprising:
- detecting an increase in the expression level of at least one retrotransposon in a sample obtained from the subject, and wherein the retrotransposon is selected from the retrotransposons HERV9-int/AluY (chr12), L1M4 (chr13), MSTA/MSTA-int (chr13), MLT1G3 (chr13), MER57E1 (chr13), MER61-int/MER61A (chr13), L1PB3 (chr13), AluSx3 (chr14), L1ME3Cz (chr14), L1MC4a (chr14), LTR16C (chr14), MIRb/AluSz (chr16), L1PA17/MLT2E (chr16), MamGypsy2-I (chr16), L1PA5 (chr18), LTR1A2 (chr18), THE1A (chr18), THE1B/AluYe5 (chr18), MIRb (chr2), THE1C (chr2), L1ME4a/L2a (chr20), LTR67B (chr20), L1MCa (chr21), L4_A_Mam (chr22), MLT1A1 (chr22), PRIMA41-int (chr22), ERVL-B4-int (chr3), L1PREC2 (chr3), L1MD1/L1M1 (chr3), L2a (chr3), THE1D (chr4), THE1B (chr4), L1MC3 (chr4), MLT2C1 (chr5), L1PREC2 (chr5), L1MB8 (chr5), MLT1E2/MLT2B3 (chr5), L1MB2 (chr5), L1MB4 (chr5), L1M4b (chr1), MSTD/AluSq2 (chr5), MLT1J1-int (chr6), L1M5/AluSc (chr7), THE1A/L1PA16 (chr7), L1PB4_1 (chr9), L1PB4_2 (chr9), L1MA6/MER4B (chr10), L2 (chrX), L1MC5 (chr10), and L2b/FLAM_A (chr11), all as defined in Table 3;
- and/or further selected from the retrotransposons IncRNA1 (chr22), MIRb (chr18), MIRb (chrX), L1MC2 (chr4), LTR12C (chrX), AmnSINE1 (chrX), IncRNA2 (chrX), MLT1C (chr5), THE1C (chr4), LTR12C (chr5), IncRNA3 (chr13), AluSx1 (chr10), all as defined in Table 5;
- and wherein the increased expression level of the retrotransposon in the sample is relative to the expression level of the same retrotransposon in a control sample or compared to a standard value.
A method of measuring tumor response to immunotherapy or to immunogenic therapy in a subject, the method comprising:
- the step of
- detecting an decrease in the expression level of at least one retrotransposon in a sample obtained from the subject, and wherein the retrotransposon is selected from the retrotransposons HERV9-int/AluY (chr12), L1M4 (chr13), MSTA/MSTA-int (chr13), MLT1G3 (chr13), MER57E1 (chr13), MER61-int/MER61A (chr13), L1PB3 (chr13), AluSx3 (chr14), L1ME3Cz (chr14), L1MC4a (chr14), LTR16C (chr14), MIRb/AluSz (chr16), L1PA17/MLT2E (chr16), MamGypsy2-I (chr16), L1PA5 (chr18), LTR1A2 (chr18), THE1A (chr18), THE1B/AluYe5 (chr18), MIRb (chr2), THE1C (chr2), L1ME4a/L2a (chr20), LTR67B (chr20), L1MCa (chr21), L4_A_Mam (chr22), MLT1A1 (chr22), PRIMA41-int (chr22), ERVL-B4-int (chr3), L1PREC2 (chr3), L1MD1/L1M1 (chr3), L2a (chr3), THE1D (chr4), THE1B (chr4), L1MC3 (chr4), MLT2C1 (chr5), L1PREC2 (chr5), L1MB8 (chr5), MLT1E2/MLT2B3 (chr5), L1MB2 (chr5), L1MB4 (chr5), L1M4b (chr1), MSTD/AluSq2 (chr5), MLT1J1-int (chr6), L1M5/AluSc (chr7), THE1A/L1PA16 (chr7), L1PB4_1 (chr9), L1PB4_2 (chr9), L1MA6/MER4B (chr10), L2 (chrX), L1MC5 (chr10), and L2b/FLAM_A (chr11), all as defined in Table 3;
- and/or further selected from the retrotransposons IncRNA1 (chr22), MIRb (chr18), MIRb (chrX), L1MC2 (chr4), LTR12C (chrX), AmnSINE1 (chrX), IncRNA2 (chrX), MLT1C (chr5), THE1C (chr4), LTR12C (chr5), IncRNA3 (chr13), AluSx1 (chr10), all as defined in Table 5;
- and wherein the decrease in the expression level of the retrotransposon in the sample relative to the expression level of the same retrotransposon in a sample obtained from the subject prior to immunotherapy or immunogenic therapy or in a sample obtained at an earlier time-point during immunotherapy or immunogenic therapy.
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Dependencies are inferred from the claim text.