IP Library › Granted Patent US 12,559,802
Granted Patent B2
US 12,559,802 · App. 18/394,161 · Granted Feb 24, 2026

Genomic alterations in the tumor and circulation of pancreatic cancer patients

Inventors: Victor Velculescu (Dayton, MD); Mark Sausen (Baltimore, MD); Vilmos Adleff (Baltimore, MD); Jillian Phallen (Baltimore, MD)
Assignee: The Johns Hopkins University
C12Q1/6886C12Q1/6816C12Q1/6827C12Q2600/106C12Q2600/112C12Q2600/118C12Q2600/156
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,559,802
App. No.
18/394,161
Granted
Feb 24, 2026
Kind
B2
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 (10)

1 . A method for characterizing and treating a pancreatic adenocarcinoma, comprising:

identifying the presence of a somatic mutation in a sample of nucleic acids from a human diagnosed with pancreatic adenocarcinoma,

wherein the somatic mutation is selected from the group consisting of: chr11_117854039-117854039_G_C 1161C>S substitution nonsynonymous coding; and chr11_117847769-117847769_C_A 229P>T substitution nonsynonymous coding;

wherein the somatic mutation is with respect to the reference human genome assembly hg18; and

wherein upon identifying the presence of the somatic mutation, performing surgery to remove the pancreatic adenocarcinoma.

2 . The method of claim 1 wherein the somatic mutation is detected by testing nucleic acids from a tissue of the human which is not pancreatic adenocarcinoma.

3 . The method of claim 1 , further comprising, wherein upon identifying the presence of the somatic mutation, decreasing the intensity of therapy for the human.

4 . The method of claim 1 , further comprising, wherein upon identifying the absence of the somatic mutation, providing to the human a prediction of decreased overall survival and decreased progression free survival, relative to humans with the somatic mutation.

5 . The method of claim 1 , further comprising, wherein upon identifying the absence of the somatic mutation, increasing the intensity of therapy for the human.

6 . The method of claim 1 wherein the sample is from a body fluid that drains from pancreata.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 12, 2024
From: VELCULESCU, VICTOR; SAUSEN, MARK; ADLEFF, VILMOS; PHALLEN, JILLIAN
To: THE JOHNS HOPKINS UNIVERSITY
Reel/Frame 066116/0332 →
Continuity (5)
Continuation 18135534 · Apr 17, 2023
Continuation 17080201 · Oct 26, 2020
Division 15552076
Provisional Application 62118604 · Feb 20, 2015
Related Publication 20240425906A1 · Dec 26, 2024
References Cited (46)
US 6399364B1 · Reeve et al. · 2002 [cited by applicant]
US 6582908B2 · Fodor · 2003 [cited by applicant]
US 10815522B2 · Velculescu · 2020 [cited by applicant]
US 20130210900A1 · Vogelstein et al. · 2013 [cited by applicant]
US 20180155770A1 · Velculescu · 2018 [cited by applicant]
US 20210108256A1 · Velculescu et al. · 2021 [cited by applicant]
NCBI database for the KMT2A gene. “KMT2A lysine methyltransferase 2A [ [cited by examiner]
NCBI dbSNP for rs2134287182, National Center for Biotechnology Information, National Library of Medicine, NIH, available via URL: < ncbi.nlm.nih.gov/snp/rs2134287168#variant_details>, printed on Jun. 25, 2025 (Year: 202… [cited by examiner]
NCBI dbSNP for rs143998546, National Center for Biotechnology Information, National Library of Medicine, NIH, available via URL: < ncbi.nlm.nih.gov/snp/rs143998546#variant_details>, printed Jun. 25, 2025 (Year: 2025). [cited by examiner]
Biankin et al Nature. Nov. 2012. 491: 399-405 and partial printout of Supplementary Table 4 that includes the entry “2108” / MLL gene, available via URL: < nature.com/articles/nature11547#Sec13>). (Year: 2012). [cited by examiner]
Jones et al (Science. 321: 1801-1806, Supporting Online Material p. 1-15, and Supplemental Table S3, available via URL: <science.org/doi/full/10.1126/science.1164368>). (Year: 2008). [cited by examiner]
Balakrishnan et al., Novel somatic and germline mutations in cancer candidate genes in glioblastoma, melanoma, and pancreatic carcinoma Cancer Research, vol. 67, No. 8, pp. 3545-3550 (2007) See abs tract: pp. 3545-3547:… [cited by applicant]
Balbas-Martinez et al., “Correction: ARIDIA Alterations Are Associated with FGFR3-Wild Type, Poor-Prognosis, Urothelial Bladder Tumors,” PLoS One, May 2013, 8(5):e62483. [cited by applicant]
Bettegowda, C. et al. “Detection of circulating tumor DNA in early- and late-stage human malignancies,” Sci Transl Med 6, 224ra24 (2014). [cited by applicant]
Biankin, A.V. et al., “Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes,” Nature 491, 399-405 (2012). [cited by applicant]
Cooper, G.M. et al., “Distribution and intensity of constraint in mammalian genomic sequence,” Genome Res 15, 901-13 (2005). [cited by applicant]
Fogelman, D.R. et al. Evidence for the efficacy of Iniparib, a PARP-1 inhibitor, in BRCA2-associated pancreatic cancer. Anticancer Res 31, 1417-20 (2011). [cited by applicant]
Fong, P.C. et al., “Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers,” N Engl J Med 361, 123-34 (2009). [cited by applicant]
Forbes, S.A. et al. “COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer” Nucleic Acids Res 39, D945-50 (2011). [cited by applicant]
Free Dictionary definition for “Testing,” available via URL: <.thefreedictionary.com/testing>, printed on Nov. 26, 2018. [cited by applicant]
Goyama et al., “ NF-KB: A Coordinator for Epigenetic Regulation by MLL,” Cancer Cell 24, 401-2 (2013). [cited by applicant]
Gupta et al., “Abstract 2174:MLL3 act as a tumor suppressor gene in pancreatic cancer,” Cancer Research, vol. 72, Abstract No. 2174 (2012). [cited by applicant]
Gupta et al., “MLL3 act as a tumor suppressor gene in pancreatic cancer,” Cancer Research, vol. 72, Abstract No. 2174 (2012). [cited by applicant]
Iacobuzio-Donahue et al., “Genetic basis of pancreas cancer development and progression: insights from whole-exome and whole-genome sequencing,” Clin Cancer Res 18, 4257-65 (2012). [cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2016/018450, dated Aug. 8, 2016, 8 pages. [cited by applicant]
International Search Report and Written Opinion in International Application No. PCT/US2016/018450, dated Aug. 8, 2016, 11 pages. [cited by applicant]
Jiao, Y. et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331, 1199-203 (2011). [cited by applicant]
Johansen et al., Comparative circulating tumor DNA levels for KRAS mutations in patients with nonresectable pancreatic cancer Journal of Clinical Oncology, vol. 33, Supplement No. 3, Abstract No. 288 (Jan. 2015). [cited by applicant]
Jones, S. et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801-6 (2008). [cited by applicant]
Jones, S. et al., “Somatic mutations in the chromatin remodeling gene ARIDIA occur in several tumor types,” Hum Mutat 33, 100-3 (2012). [cited by applicant]
Newman et al., “An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage,” Nat Med 20, 548-54 (2014). [cited by applicant]
nih.gov [online], “NCBI SNP Database Reference Report for rs878853088,” Apr. 9, 2021, retrieved from URL<ncbi.nlm.nih.gov/snp/rs878853088#variant details>, printed Oct. 12, 2022, 8 pages. [cited by applicant]
Olsen et al. Am J Clinical Oncology. 2009. 32(2): 115-121. [cited by applicant]
Paulson et al., “Therapeutic advances in pancreatic cancer,” Gastroenterology, 144, 1316-26 (2013). [cited by applicant]
Popovic et al., “Emerging epigenetic targets and therapies in cancer medicine,” Cancer Discov, 2(5), 405-13 (2012). [cited by applicant]
Ramanathan, R.K. et al. Low overexpression of HER-2/neu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin) and irinotecan as therapy. A phase II Trial. Cancer Invest 22, 858-65 (2004). [cited by applicant]
Sausen et al., “Clinical Implications of genomic alterations in the tumour and circulation of pancreatic cancer patients,” Nature Communications vol. 6. No. 7686 (2015). [cited by applicant]
Sausen, M. et al., “Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma,” Nat Genet 45, 12-7 (2013). [cited by applicant]
Shain et al., “Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer,” PNAS, vol. 109, No. 5, pp. E252-E259 (201… [cited by applicant]
Siegel et al., “Cancer statistics, 2013,” CA Cancer J Clin 63, 11-30 (2013). [cited by applicant]
Siegel et al., “Cancer statistics, 2015,” CA Cancer J Clin 65, 5-29 (2015). [cited by applicant]
Sorscher, S.M. Marked response to single agent trastuzumab in a patient with metastatic HER-2 gene amplified rectal cancer. Cancer Invest 29, 456-9 (2011). [cited by applicant]
Uemura et al.J Gastroenterol 2004. 39: 56-60. [cited by applicant]
Van der Heijden, M.S. et al., “In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor,” Clin Cancer Res 11, 7508-15 (2005). [cited by applicant]
Villrumnel, M.C. et al., “Personalizing cancer treatment in the age of global genomic analyses: P ALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer,” Mol Cancer Ther, 10, 3-8 (2011). [cited by applicant]
Wang et al., Whole-exome sequencing of human pancreatic cancers and characterization of genomic instability caused by MLH1 haploinsufficiency and complete deficiency, Genome Research, vol. 22, pp. 208-219 (2012). [cited by applicant]