The task to identify whether an archival malignant tumor specimen had been mislabeled or interchanged is a challenging one for forensic genetic&The nuclear DNA(nDNA)markers were affected by the aberration of tumor...The task to identify whether an archival malignant tumor specimen had been mislabeled or interchanged is a challenging one for forensic genetic&The nuclear DNA(nDNA)markers were affected by the aberration of tumor cells,so they were not suitable for personal identification when the tumor tissues were tested.In this study,we focused on a new solution-mitochondrial single nucleotide polymorphism(mtSNP)haplotyping by a multiplex SNaPshot assay.To validate our strategy of haplotyping with 25 mtSNPs,we analyzed 15 pairs of cancerous/healthy tissues taken from patients with ductal breast carcinoma.The haplotypes of all the fifteen breast cancer tissues were matched with their paired breast tissues.The heteroplasmy at 2 sites,14783A/G and 16519C/T was observed in one breast tissue,which indicated a mixture of related mitochondrial haplotypes.However,only one haplotype was retained in the paired breast cancer tissue,which could be considered the result of proliferation of tumor subclone.The allele drop-out and allele drop-in were observed when 39 STRs and 20 tri-allelic SNPs of nDNA were applied.Compared to nDNA markers applied,25 mtSNPs were more stable without interference from aberrance of breast cancer.Also,two cases were presented where the investigation of haplotype with 25 mtSNPs was used to prove the origin of biopsy specimen with breast cancer.The mislabeling of biopsy specimen with breast cancer could be certified in one case but could not be supported in the other case.We highlight the importance of stability of mtSNP haplotype in breast cancer.It was implied that our multiplex SNaPshot assay with 25 mtSNPs was a useful strategy to identify mislabeled breast cancer specimen.展开更多
基金supported by the grants from the Five-twelfth National Science and Technology Support Program of China(2012BAK16B01)from the National Natural Science Foundation of China(81330073).
文摘The task to identify whether an archival malignant tumor specimen had been mislabeled or interchanged is a challenging one for forensic genetic&The nuclear DNA(nDNA)markers were affected by the aberration of tumor cells,so they were not suitable for personal identification when the tumor tissues were tested.In this study,we focused on a new solution-mitochondrial single nucleotide polymorphism(mtSNP)haplotyping by a multiplex SNaPshot assay.To validate our strategy of haplotyping with 25 mtSNPs,we analyzed 15 pairs of cancerous/healthy tissues taken from patients with ductal breast carcinoma.The haplotypes of all the fifteen breast cancer tissues were matched with their paired breast tissues.The heteroplasmy at 2 sites,14783A/G and 16519C/T was observed in one breast tissue,which indicated a mixture of related mitochondrial haplotypes.However,only one haplotype was retained in the paired breast cancer tissue,which could be considered the result of proliferation of tumor subclone.The allele drop-out and allele drop-in were observed when 39 STRs and 20 tri-allelic SNPs of nDNA were applied.Compared to nDNA markers applied,25 mtSNPs were more stable without interference from aberrance of breast cancer.Also,two cases were presented where the investigation of haplotype with 25 mtSNPs was used to prove the origin of biopsy specimen with breast cancer.The mislabeling of biopsy specimen with breast cancer could be certified in one case but could not be supported in the other case.We highlight the importance of stability of mtSNP haplotype in breast cancer.It was implied that our multiplex SNaPshot assay with 25 mtSNPs was a useful strategy to identify mislabeled breast cancer specimen.
