Nucleic acid probes

A composition, comprising:

• a plurality of oligonucleotide probes capable of hybridizing to target nucleic acid fragments of cancer gene exons, introns, promoters, and external regions surrounding cancer genes resulting from nucleic acid fragmentation of a nucleic acid sample, wherein:
• a plurality of external region directed oligonucleotide probes capable of hybridizing to target nucleic acid fragments from external regions comprises (i) a set of probe pairs each capable of hybridizing to a target nucleic acid fragment of about 260 consecutive nucleotides or longer, and (ii) a set of single oligonucleotide probes each capable of hybridizing to a nucleic acid fragment of about 130 consecutive nucleotides to about 260 consecutive nucleotides in length;
• the external region directed oligonucleotide probes in the set of oligonucleotide probe pairs and the set of single oligonucleotide probes comprise a polynucleotide (i) about 110 to about 130 consecutive nucleotides in length, (ii) substantially complementary to a subsequence of a nucleic acid fragment, (iii) containing an average GC content of about 40 percent to about 60 percent, and (iv) complementary to a subsequence of a nucleic acid that does not repeat in the nucleic acid fragments;
• each of the oligonucleotide probe pairs in the set of oligonucleotide probe pairs comprises (i) a first oligonucleotide probe comprising a 5′ end about 2 to about 15 consecutive nucleotides from the 5′ end of the fragment, and (ii) a second oligonucleotide probe comprising a 3′ end about 2 to about 15 consecutive nucleotides from the 3′ end of the nucleic acid fragment to which the first oligonucleotide probe of the probe pair is capable of hybridizing;
• and
• each oligonucleotide probe in the set of single oligonucleotide probes comprises a 5′ or 3′ end about 2 to about 15 consecutive nucleotides from the 5′ end of a nucleic acid fragment.

A method for nucleic acid enrichment, comprising:

• subjecting target nucleic acid from a nucleic acid sample to nucleic acid cleavage conditions in which nucleic acid fragments are generated;
• subjecting the target nucleic acid fragments to linking conditions in which proximity ligated nucleic acid molecules are generated;
• contacting the proximity ligated nucleic acid molecules (or amplified copies thereof) with a composition comprising a plurality of oligonucleotide probes under hybridization conditions in which hybridization complexes comprising proximity ligated nucleic acid hybridized to oligonucleotide probes are generated;
• isolating the complexes;
• analyzing nucleic acid in the complexes, and;
• wherein plurality of oligonucleotide probes capable of hybridizing to target nucleic acid fragments of cancer gene exons, introns, promoters, and external regions surrounding cancer genes resulting from nucleic acid fragmentation of a nucleic acid sample comprise
• a plurality of external region directed oligonucleotide probes capable of hybridizing to target nucleic acid fragments from external regions comprises (i) a set of probe pairs each capable of hybridizing to a target nucleic acid fragment of about 260 consecutive nucleotides or longer, and (ii) a set of single oligonucleotide probes each capable of hybridizing to a nucleic acid fragment of about 130 consecutive nucleotides to about 260 consecutive nucleotides in length;
• the external region directed oligonucleotide probes in the set of oligonucleotide probe pairs and the set of single oligonucleotide probes comprise a polynucleotide (i) about 110 to about 130 consecutive nucleotides in length, (ii) substantially complementary to a subsequence of a nucleic acid fragment, (iii) containing an average GC content of about 40 percent to about 60 percent, and (iv) complementary to a subsequence of a nucleic acid that does not repeat in the nucleic acid fragments;
• each of the oligonucleotide probe pairs in the set of oligonucleotide probe pairs comprises (i) a first oligonucleotide probe comprising a 5′ end about 2 to about 15 consecutive nucleotides from the 5′ end of the fragment, and (ii) a second oligonucleotide probe comprising a 3′ end about 2 to about 15 consecutive nucleotides from the 3′ end of the nucleic acid fragment to which the first oligonucleotide probe of the probe pair is capable of hybridizing;
• and
• each oligonucleotide probe in the set of single oligonucleotide probes comprises a 5′ or 3′ end about 2 to about 15 consecutive nucleotides from the 5′ end of a nucleic acid fragment.