NB-UVB Phototherapy Mutation Burden Cohort (Fowler et al. 2025)

Overview

Cohort of 16 patients with psoriasis recruited at a single UK dermatology centre providing paired pre- and post-treatment skin biopsies to quantify somatic mutation burden induced by a single course of narrowband ultraviolet B (NB-UVB) phototherapy. Profiled by NanoSeq (nanorate duplex sequencing) on epidermal DNA microdissected from 6-mm punch biopsies of buttock (infrequently sun-exposed) and dorsal forearm (frequently sun-exposed) skin.

Note: This dataset is registered under the studyId bcc_unige_2016 in the wiki ontology but is not hosted on cBioPortal. Sequencing data are deposited at the European Genome-Phenome Archive (EGA): whole-genome data under EGAD0000101525 and NanoSeq data under EGAD00001015249; HaCaT keratinocyte ancillary data at ENA accession ERP156525. PMID:26950094

Composition

  • 21 patients with psoriasis recruited; 16 provided paired pre/post NB-UVB biopsies (6 women, 10 men; median age 33, range 20–73).
  • UK census ethnicity: 13 White British, 1 White Irish, 1 Asian Indian, 1 Asian other.
  • 6-mm punch biopsies from buttock (infrequently sun-exposed, n=14 paired) and dorsal forearm (frequently sun-exposed, n=10 paired); venous blood used as germline reference.
  • NB-UVB delivered at 311 nm; 14–35 exposures (median 28); total course dose 84–756 SED (median 219); MED 1.7–5.1 SED (median 2.9).
  • Epidermal DNA isolated by microdissection; ~one-third of the genome covered per NanoSeq library — sufficient for mutation-burden / signature analysis but not for driver-gene calling.
  • Ancillary in vitro: HaCaT keratinocytes treated with 8-methoxypsoralen (methoxsalen) plus UVA, then re-sequenced with NanoSeq to validate a PUVA-associated signature. PMID:26950094

Assays / panels (linked)

  • nanoseq — duplex sequencing with error rate <5 per billion bp; ~one-third-genome coverage per sample (paired pre/post NB-UVB biopsies).
  • whole-genome-seq — whole-genome NanoSeq libraries (EGA EGAD0000101525).

Papers using this cohort

  • PMID:26950094 — Fowler et al., Br J Dermatol 2025: primary study quantifying NB-UVB-induced mutation burden in normal skin and modelling skin-cancer surveillance thresholds.

Notable findings derived from this cohort

  • Single NB-UVB course raised median mutation burden in buttock skin from 0.52 to 1.09 substitutions/Mb (P < 0.001) and in forearm skin from 3.13 to 3.77 substitutions/Mb (P = 0.01) PMID:26950094.
  • Dose-normalised burden (Δ-mutation burden/dose): median 0.0021 substitutions/Mb/SED (buttock) and 0.0034 (forearm); UVR-associated COSMIC signatures SBS7a/SBS7b appeared in all post-NB-UVB samples PMID:26950094.
  • Prior phototherapy elevated baseline mutation burden (P = 0.01), indicating induced mutations persist across decades PMID:26950094.
  • Asian patients had lower Δ-mutation burden/dose (median 0.0003 substitutions/Mb/SED), correlated with polygenic tan-propensity scores PMID:26950094.
  • Surveillance modelling (for MED = 2 SED): cancer surveillance should begin after 422 (cautious), 165 (typical), or 58 (enthusiastic sun-exposure) NB-UVB exposures — far below the current BAD/BPG 500-exposure guideline threshold PMID:26950094.

Sources

  • Not on cBioPortal. Data deposited at:
    • EGA (whole-genome): EGAD0000101525
    • EGA (NanoSeq): EGAD00001015249
    • ENA (HaCaT ancillary data): ERP156525
  • PMID:26950094 — Fowler JC et al., “Mutation burden of narrowband ultraviolet B phototherapy (NB-UVB) in human skin: relevance to NB-UVB lifetime exposures and skin cancer surveillance.” Br J Dermatol 2025.

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