Genomic alterations in the tumor and circulation of pancreatic cancer patients
Abstract
Pancreatic adenocarcinoma has the worst overall mortality of any solid tumor, with only 7% of patients surviving after 5 years. To evaluate the clinical implications of genomic alterations in this low cellularity tumor type, we deeply sequenced the genomes of 101 enriched pancreatic adenocarcinomas from patients who underwent potentially curative resections and used non-invasive approaches to examine tumor specific mutations in the circulation of these patients. These analyses revealed somatic mutations in chromatin regulating genes including MLL and ARID1A in 20% of patients that were associated with improved survival. Liquid biopsy analyses of cell free plasma DNA revealed that 43% of patients with localized disease had detectable circulating tumor DNA (ctDNA) in their blood at the time of diagnosis. Detection of ctDNA after resection predicted clinical relapse and poor outcome, and disease recurrence by ctDNA was detected 6.5 months earlier than with standard CT imaging.
Claims
exact text as granted — not AI-modified1 - 11 . (canceled)
12 . A probe or primer specific for a mutant chromatin regulating MLL (chromosome 11), MLL2 (chromosome 12), MLL 3 (chromosome 7) or ARID1A gene, said probe or primer comprising a mutation selected from the group consisting of:
ARID1A mutations:
chr1_26928798-
403Q > X
Substitution
Nonsense;
26928798_C_T
chr1_26979465-
NA
Insertion
Frameshift;
26979465_C
chr1_26978312-
1779E > G
Substitution
Nonsynonymous
26978312_A_G
coding;
chr1_26978589-
1871H > Q
Substitution
Nonsynonymous
26978589_C_G
coding;
chr1_26895595-
38E > EA
Insertion
In-frame
26895595_GGC
insertion;
chr1_26960135-
708Q > X
Substitution
Nonsense;
26960135_C_T
chr1_26973560-
1419A > T
Substitution
Nonsynonymous
26973560_G_A
coding;
chr1_26974706-
1682A > E
Substitution
Nonsynonymous
26974706_C_A
coding;
chr1_26972534-
1276R > X
Substitution
Nonsense;
26972534_C_T
chr1_26978518-
NA
Deletion
Frameshift;
26978518_G —
chr1_26979254-
NA
Insertion
Frameshift;
26979254_TT
and MLL (chromosome 11), MLL2 (chromosome 12), or MLL 3 (chromosome 7) mutations:
chr7_151490485-
3704V > L
Substitution
Nonsynonymous
151490485_C_G
coding;
chr11_117854039-
1161C > S
Substitution
Nonsynonymous
117854039_G_C
coding;
chr11_117847769-
229P > T
Substitution
Nonsynonymous
117847769_C_A
coding;
chr12_47718147-
3087R > W
Substitution
Nonsynonymous
47718147_G_A
coding;
chr7_151515732-
NA
Substitution
Splice site donor;
151515732_C_T
chr12_47729834-
NA
Insertion
Frameshift;
47729834_A
chr7_151576224-
743P > L
Substitution
Nonsynonymous
151576224_G_A
coding;
chr7_151476195-
4584R > W
Substitution
Nonsynonymous
151476195_G_A
coding;
chr7_151686622-
NA
Insertion
Frameshift;
151686622_TC
chr12_47711653-
NA
Insertion
Frameshift;
47711653_T
chr12_47731362-
NA
Deletion
Frameshift;
47731362_G —
chr7_151601824-
NA
Insertion
Frameshift;
151601824_T
chr12_47722327-
1974T > M
Substitution
Nonsynonymous
47722327_G_A
coding; and
chr7_151510210-
1890R > X
Substitution
Nonsense.
151510210_G_A
13 . The probe or primer of claim 12 which is labeled with a radionuclide, a fluorescent label, or a chromophore.
14 - 34 . (canceled)Join the waitlist — get patent alerts
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