Topographic genotyping for determining the diagnosis, malignant potential, and biologic behavior of pancreatic cysts and related conditions
AssigneeInterpace Diagnostics Corporation
InventorsSydney David Finkelstein, Patricia Swalsky
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Abstract
The application relates to a method of a predicting the presence of invasive pancreatic cancer or high grade dysplasia, pre-cancerous pancreatic states and non-neoplastic conditions comprising detailed molecular analysis incorporating DNA quality and quantity, K-ras mutational analysis and a broad spectrum of tumor suppressor gene linked microsatellite LOH. Methods of diagnosing, determining prognosis of and determining a course of treatment for pancreatic cancer or high grade dysplasia, pre-cancerous pancreatic states and non-neoplastic conditions are also provided.
Claims20
A method for predicting the presence of a pancreatic anomaly in a patient suffering from pancreatic cysts comprising:
- a) performing molecular analysis of DNA from an aspirate from a patient pancreatic cyst comprising
- (i) performing an optical density analysis of the aspirate to determine DNA quantity;
- (ii) performing a quantitative PCR analysis of the aspirate to determine DNA quality;
- (iii) performing competitive template PCR to determine DNA quality;
- and
- b) performing mutation analysis of the DNA in the aspirate comprising:
- (i) determining the presence of mutations in D1S407, D1S1193, LMYC, D1S1172, D3S1539, D3S2303, or D5S592;
- (ii) determining tumor suppressor gene loss of heterozygosity (LOH) by analyzing polymorphic microsatellites or other polymorphic markers linked to tumor suppressor genes with respect to their allelic balances, wherein the tumor suppressor genes are selected from the group consisting of:
- VHL, APC, P53, PTEN, and P16;
- (iii) determining point mutations in the K-ras oncogene and/or point mutations in at least one other cancer-associated gene;
- (iv) determining other structural alterations in the DNA;
- (v) determining the percentage of mutated DNA from steps b)(ii) and b)(iii);
- and
- (vi) determining the specific temporal sequence of mutation accumulation based on step (v), wherein the temporal sequence of mutation accumulation is predictive of the presence of a pancreatic anomaly.
A method for diagnosing and/or determining the prognosis of a pancreatic anomaly in a patient suffering from pancreatic cysts comprising:
- a) performing molecular analysis of DNA from an aspirate from a patient pancreatic cyst comprising
- (i) performing an optical density analysis of the aspirate to determine DNA quantity;
- (ii) performing a quantitative PCR analysis ofthe aspirate to determine DNA quality;
- (iii) performing competitive template PCR to determine DNA quality;
- and
- b) performing mutation analysis of the DNA in the aspirate comprising:
- (i) determining the presence of one or more mutations in a tumor suppressor gene and/or the presence of a cancer related genetic marker;
- (ii) determining tumor suppressor gene loss of heterozygosity (LOH) by analyzing polymorphic microsatellites or other polymorphic markers linked to tumor suppressor genes with respect to their allelic balances;
- (iii) determining point mutations in the K-ras oncogene and/or point mutations in at least one other cancer-associated gene;
- (iv) determining other structural alterations in DNA;
- (v) determining the percentage of mutated DNA from steps b)(ii) and b)(iii);
- and
- (vi) determining the specific temporal sequence of mutation accumulation based on step v), and diagnosing and/or determining the prognosis of a pancreatic anomaly of the patient in need based on the results of steps a) and b).
A method for determining a course of treatment for a pancreatic anomaly in a patient suffering from pancreatic cysts comprising:
- a) performing molecular analysis of DNA from an aspirate from a patient pancreatic cyst comprising:
- (i) performing an optical density analysis of the aspirate to determine DNA quantity;
- (ii) performing a quantitative PCR analysis of the aspirate to determine DNA quality;
- and
- (iii) performing competitive template PCR to determine DNA quality;
- and
- b) performing mutation analysis of the DNA in the aspirate comprising:
- (i) determining the presence of mutations in a tumor suppressor gene and/or the presence of a cancer related genetic marker;
- (ii) determining tumor suppressor gene loss of heterozygosity (LOH) by catalyzing polymorphic microsatellites or other polymorphic markers linked to tumor suppressor genes with respect to their allelic balances;
- (iii) determining point mutations in the K-ras oncogene and/or point mutations in at least one other cancer-associated gene;
- (iv) determining other structural alterations in DNA;
- (v) determining the percentage of mutated DNA from steps b)(ii) and b)(iii);
- and
- (vi) determining the specific temporal sequence of mutation accumulation based on step v), wherein the results of steps a) and b) are used to determine a course of therapy for a patient suffering from a pancreatic anomaly.
Dependencies are inferred from the claim text.