Ductal and acinar components of mixed prostatic adenocarcinoma frequently have a common clonal origin

Abstract

Background Ductal adenocarcinoma (DA) is an aggressive subtype of prostate cancer. It is most commonly seen in mixed tumors together with conventional acinar adenocarcinoma (AA). The genetic profile of DA and its clonal origin is not fully characterized. Objective To investigate whether DA represents a distinct genetic subtype and to investigate the somatic relationship between the ductal and acinar components of mixed cancers. Design, Setting, and Participants In 17 radical prostatectomy specimens ductal and acinar tumor components from the same tumor foci were dissected. DNA was extracted and genomic sequencing performed. After exclusion of two cases with low cell yield, 15 paired samples remained for analysis. Results In 12 of 15 cases a common somatic denominator was identified, while three cases had clonally separate components. In DA, TMPRSS2‐ERG gene fusions were detected in 47% (7/15), clonal FOXA1 alterations in 33% (5/15) and SPOP alterations in 27% (4/15) of cases. In one case KIAA1549−BRAF fusion was identified. Genome doubling events, resulting in an increased ploidy, were identified in the DA in 53% (8/15) of cases, but not seen in any AA. PTEN and CTNNB1 alterations were enriched in DA (6/15) but not seen in any AA. No cancers showed microsatellite instability or high tumor mutation burden. Conclusions Ductal and acinar prostate adenocarcinoma components of mixed tumors most often share the same origin and are clonally related. DA components in mixed tumor often exhibit genome doubling events resulting in aneuploidy, consistent with the aggressive nature of high grade prostate cancer.

Genomic analysis of aggressive ductal adenocarcinoma of the prostate

“…However, the rates of TP53 alterations in ductal adenocarcinoma was only 18% in the largest series (51 tumors) 7 . Cases with RB1 alterations have not been reported by major case series or a recent study of 15 cases limited to mixed‐type ductal adenocarcinomas with a common clonal origin 22 . The only case report of PTEN and RB1 co‐loss, and TP53 somatic mutation (p.R249G) has already been reported 13 .…”

“… 7 Cases with RB1 alterations have not been reported by major case series or a recent study of 15 cases limited to mixed‐type ductal adenocarcinomas with a common clonal origin. 22 The only case report of PTEN and RB1 co‐loss, and TP53 somatic mutation (p.R249G) has already been reported. 13 These results of this study are very different from those reported in the United States and Western Europe, where TP53 alterations are low and RB1 alterations are absent, suggesting that TP53 and RB1 alterations may be more common in Asian patients with ductal adenocarcinoma and may have more aggressive characteristics.…”

Current State of Artificial Intelligence (AI) in Oncology: A Review

“…On July 21, 2022, FDA approved the commercialization of software to aid pathologists in detecting suspected cancer spots in digitally scanned histology plates or slides of prostate biopsies [22]. Prostate biopsies would be facilitated by this program.…”

Genetic identification and phylogenetic relationships of fish species at Panjnad , Abbasia and Abu Dahbi canals (Punjab, Pakistan) based on mitochondrial COI sequences

“…On July 21, 2022, FDA approved the commercialization of software to aid pathologists in detecting suspected cancer spots in digitally scanned histology plates or slides of prostate biopsies [22]. Prostate biopsies would be facilitated by this program.…”