Detection processes using sites of chromosome interaction
A process for analysing epigenetically active regions of the genome.
1. A method for selecting a human individual who is responsive to anti-PD-1, anti-PD-L1 or anti-PD1-1/anti-PD-L1 combined therapy for melanoma and treating the selected human individual, the method comprising selecting the human individual by determining in a sample from the individual the presence or absence of a first, second, third, fourth, fifth, sixth, seventh, and eighth chromosome interaction,
wherein selecting of the human individual as responsive to anti-PD-1, anti-PD-L1 or anti-PD1-1/anti-PD-L1 combined therapy for melanoma is based on detection of:
presence of the first chromosome interaction,
absence of the second chromosome interaction,
presence of the third chromosome interaction,
presence of the fourth chromosome interaction,
absence of the fifth chromosome interaction,
absence of the sixth chromosome interaction,
presence of the seventh chromosome interaction,
absence of the eighth chromosome interaction, and treating the selected human individual for melanoma by administering to the selected human individual anti-PD-1, anti-PD-L1 or anti-PD1-1/anti-PD-L1 combined therapy,
wherein said determining the presence or absence of the chromosome interactions is carried out by
(a) cross-linking of chromosome regions in the sample which have come together in a chromosome interaction;
(b) subjecting said cross-linked regions to cleavage;
(c) ligating said cross-linked cleaved DNA ends to form ligated nucleic acids; and
(d) detecting the presence or absence of the ligated nucleic acids to thereby detect whether regions have been brought together in a chromosome interaction;
wherein:
the ligated nucleic acid corresponding to the first chromosome interaction is detected by the probe sequence:
TGTAAACTGTAATATCAAAAATTCAAAATCGAAGAGTTGATTTACTTATTAACATTA GAA (SEQ ID NO: 734);
the ligated nucleic acid corresponding to the second chromosome interaction is detected by the probe sequence:
ACTT-TATAGTGAAAAGTGCCATTTGAGTCGACTGTGATTGAATGTAAAAGGTTTTA AAT (SEQ ID NO: 735);
the ligated nucleic acid corresponding to the third chromosome interaction is detected by the probe sequence:
TACTGTAGTAAGTTCTCTGAGGAGGATATCGAAGTCTTGGATTAAGGTTCATTCAAC AAA (SEQ ID NO: 736);
the ligated nucleic acid corresponding to the fourth chromosome interaction is detected by the probe sequence:
TTCCATAGATTACTTTTCAAATCATCCTTCGAAGCTGGCGGCTGAGGGCCCGGCGCC AAG (SEQ ID NO: 741);
the ligated nucleic acid corresponding to the fifth chromosome interaction is detected by the probe sequence:
TCCATTTGAAGGATGAGAAAACTGAGGCTCGAGGCTTAGAAAGTTTCATTTGGTTGC TCA (SEQ ID NO: 737);
the ligated nucleic acid corresponding to the sixth chromosome interaction is detected by the probe sequence:
TTTTAAACCCAGGTGCACACACAAGAGCTCGAAGCAGGAATCCTGGTTCTGTTCCCA GGC (SEQ ID NO: 738);
the ligated nucleic acid corresponding to the seventh chromosome interaction is detected by the probe sequence:
CCACTCCCCCAGGCTTACCTGCGAGCCATCGAGGTGGGCCTGGGTTCTCGTGGAGGG AGA (SEQ ID NO: 739);
the ligated nucleic acid corresponding to the eighth chromosome interaction is detected by the probe sequence:
TCACTCATTCTAGATCCCTCTGTAAAGTTCGAACTCTGGACCTTGTGATCCACCCACC TT (SEQ ID NO: 740);
and wherein said human individual has melanoma.