# Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms

Source: https://onco.cc/key-papers/paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018/  
OnCo record `paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Offering a 76-gene inherited-risk test to 615 consecutive pancreatic tumour patients at Memorial Sloan Kettering found a pathogenic variant in one in five, more than 40% of whom would not have qualified for testing under the guidelines of the time.

## Summary

615 unselected patients with exocrine pancreatic neoplasms consented to somatic tumour and matched normal profiling of 410 to 468 genes; germline testing of 76 susceptibility genes was performed in an identified manner in 356 and anonymised in 259. Pathogenic germline alterations were present in 122 (19.8%) across 24 genes including BRCA1/2, ATM, PALB2 and other DNA damage response genes; 41.8% did not meet then-current testing guidelines. Median overall survival did not differ by germline status (50.8 months carriers). Loss of heterozygosity was found in 60.0% of BRCA1/2 tumours. The alterations were judged therapeutically actionable in about 5 to 10% of patients.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: JNCI: Journal of the National Cancer Institute
- Year: 2018
- DOI: 10.1093/jnci/djy024
- Authors: Lowery MA, Wong W, Jordan EJ, et al.
- Findings: Pathogenic germline alteration in 19.8% of 615 on a 76-gene panel.; 41.8% of carriers outside testing guidelines; 60% of BRCA1/2 tumours showed loss of heterozygosity.
- What it means: The broad-panel figure: one patient in five carries something inheritable, and about one in fifteen carries something treatable.
- Caveats: Includes non-ductal exocrine neoplasms; 76 genes include moderate-penetrance genes.; Single tertiary centre.

## Sources

- Lowery et al., JNCI 2018: prospective germline testing of 615 exocrine pancreatic neoplasms (MSK): https://doi.org/10.1093/jnci/djy024
- PubMed: https://pubmed.ncbi.nlm.nih.gov/29506128/

## Connected records

- biomarkers: [Germline BRCA1/2 pathogenic variant (gBRCAm)](https://onco.cc/biomarkers/brca-germline/)
- cancers: [BRCA or PALB2-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/brca-palb2-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/)
- targets: [ATM](https://onco.cc/targets/atm/), [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [PALB2](https://onco.cc/targets/palb2/)
- institutions: [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- terms: [Germline BRCA mutation (gBRCA)](https://onco.cc/terms/gbrca-mutation/), [Variant of uncertain significance (VUS)](https://onco.cc/terms/vus/)
- people: [Eileen M. O'Reilly](https://onco.cc/people/eileen-oreilly/), [Maeve Lowery](https://onco.cc/people/maeve-lowery/)
- journals: [JNCI: Journal of the National Cancer Institute](https://onco.cc/journals/jnci/)

---
JSON: https://onco.cc/api/v1/entities/paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018.json