Comparison of the mutational profiles of neuroendocrine breast tumours, invasive ductal carcinomas and pancreatic neuroendocrine carcinomas.

in Oncogenesis by Peeter Karihtala, Katja Porvari, Nelli Roininen, Sari Voutilainen, Johanna Mattson, Päivi Heikkilä, Kirsi-Maria Haapasaari, Katri Selander

TLDR

  • The study compares mutational profiles of breast NETs with IDC and PNET, finding distinct variant rates in certain genes and mutational signatures.
  • The study identifies potential druggable targets for breast NET treatment.
  • Breast NETs are a separate breast cancer entity, but their optimal treatment remains unknown.

Abstract

The pathophysiology and the optimal treatment of breast neuroendocrine tumours (NETs) are unknown. We compared the mutational profiles of breast NETs (n = 53) with those of 724 publicly available invasive ductal carcinoma (IDC) and 98 pancreatic NET (PNET) cases. The only significantly different pathogenetic or unknown variant rate between breast NETs and IDCs was detected in the TP53 (11.3% in breast NETs and 41% in IDCs, adjusted p value 0.027) and ADCK2 (9.4% in breast NETs vs. 0.28% in IDCs, adjusted p value 0.045) genes. Between breast NETs and PNETs, different pathogenetic or unknown variant frequencies were detected in 30 genes. For example, MEN1 was mutated in only 6% of breast NETs and 37% in PNETs (adjusted p value 0.00050), and GATA3 pathogenetic or unknown variants were only found in 17.0% of breast NETs and 0% in PNETs (adjusted p value 0.0010). The most commonly affected oncogenic pathways in the breast NET cases were PI3K/Akt/mTOR, NOTCH and RTK-RAS pathways. Breast NETs had typically clock-like mutational signatures and signatures associated with defective DNA mismatch repair in their mutational landscape. Our results suggest that the breast NET mutational profile more closely resembles that of IDCs than that of PNETs. These results also revealed several potentially druggable targets, such as MMRd, in breast NETs. In conclusion, breast NETs are indeed a separate breast cancer entity, but their optimal treatment remains to be elucidated.

Overview

  • The study aims to explore the pathophysiology and optimal treatment of breast neuroendocrine tumours (NETs).
  • The study compares the mutational profiles of breast NETs with those of invasive ductal carcinoma (IDC) and pancreatic NET (PNET) cases.
  • The study aims to identify potentially druggable targets for breast NET treatment.

Comparative Analysis & Findings

  • The study found that TP53 and ADCK2 genes have significantly different pathogenetic or unknown variant rates between breast NETs and IDCs.
  • The study identified different pathogenetic or unknown variant frequencies between breast NETs and PNETs in 30 genes, including MEN1 and GATA3.
  • The study found that breast NETs have clock-like mutational signatures and signatures associated with defective DNA mismatch repair, resembling IDCs rather than PNETs.

Implications and Future Directions

  • The study suggests that breast NETs are a separate breast cancer entity, but their optimal treatment remains to be elucidated.
  • The study highlights the potential druggable targets, such as MMRd, for breast NET treatment.
  • Future studies should focus on exploring the optimal treatment strategies for breast NETs, taking into account their distinct mutational profile.
Read Full Article