Germline mutations affecting the proofreading domains of POLE and POLD1
predispose to colorectal adenomas and carcinomas.
In part, the trial will explore the use of PGDx's liquid biopsy assay to confirm POLE and POLD1 mutations in solid tumors and to investigate whether those tumor types are responsive to immunotherapy.
The study will evaluate the efficacy and safety of nivolumab (anti-PD-1) alone and in combination with ipilimumab (anti-CTLA-4) in patients with POLE and POLD1 mutations and will collect both blood and tumor tissue samples from patients to look at correlation between mutations detected in a tumor tissue sample and those detected from a blood test.
Some novel mutations such as POLE and POLD1
have also been identified in the CMMRD .
Other rare inherited syndromes include oligopolyposis (germline mutations in POLE and POLD1
genes), endonuclease IIIlike protein 1 (encoded by NTHL1 gene), juvenile polyposis syndrome (mutations in BMPR1A and SMAD4 genes), Cowden syndrome (mutations in PTEN gene), and Peutz-Jeghers syndrome (mutations in STK11 gene).
Ling, "Effect of Smilax china L.-containing serum on the expression of POLD1
mRNA in human hepatocarcinoma SMMC-7721 cells," Experimental and Therapeutic Medicine, vol.
PCNA and REV3L are genes that were suggested by GeneMania and showed distinct linkages with quite a few query genes such as TP53, MSH6, POLD1
, and PTEN, respectively.
The level of TCLP As in the FAP-amended soils at about pH 6 increases in the order Pod2b < Fer2 < Pod2a < Fer1 < Pold1
Recently, whole-genome sequencing of constitutional DNA from individuals diagnosed with multiple colorectal adenomas by age 60 years revealed that a germline mutation (Ser478Asn) in the POLD1
[polymerase (DNA directed), delta 1, catalytic subunit] gene, which encodes the catalytic subunit of polymerase [delta] that promotes lagging-strand synthesis during DNA replication, is linked to an inherited predisposition to both colorectal cancer and endometrial cancer (12).