METHODS: Next-generation
DNA sequencing on Ion
Proton identified unique and common missense mutations in the brain, breast and ano-
rectal tumors. All mutations were benign, and only one pathogenic mutation in p. (Cys3346Arg) found in AMM
tumor. In
phyllodes tumor of breast, two unique missense variants were detected (rs113562492) p. (Met2841Val); and (rs137972270) in p. (Arg589Cys) and these variants are not present in other
tumors tested. The variant rs137972270 was reported only in two cases sofar in ClinVar database. Missense variants such as rs115045643, rs116809571, rs115338476, and rs76895755 are found only in
PNET, and a variant rs62406032 in a-
CPP, another one rs35445653 in ATRT cases were unique for these
tumors, which are not present in other
tumors. Several synonymous and intronic variants of PKHD1 gene were also found in these
tumors. A synonymous variant p. (Asp395Asp), rs1896976 and two intronic SNPs viz., rs1326605, and rs1571084 were found in all
tumors tested. The SNP rs9395699 in IVS66 was found uniquely in IPC
breast tumor only in this study. Allele coverage, allele ratio, p-value, Phred qual score, sequencing coverage, alleles frequencies were also analysed, the p-values and Phred quality score were significantly higher.
CONCLUSION: These
tumors did not have any insertion/ deletion mutations, nonsense, or truncated mutations in it. The screening of PKHD1 gene revealed signature mutations for the solid
tumors studied by NGS method. This investigation may help in understanding these
tumor pathology at molecular level.