<i>PARP1</i> polymorphisms play opposing roles in melanoma occurrence and survival

Law, Matthew H.; Rowe, Casey; Montgomery, Grant W.; Hayward, Nicholas K.; MacGregor, Stuart; Khosrotehrani, Kiarash

doi:10.1002/ijc.29280

Cited by 7 publications

(4 citation statements)

References 9 publications

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“…The opposite effect of rs2249844 in melanoma risk and survival was further confirmed in a report by Law et al. (), where rs3219090 (a SNP that completely correlates with rs2249844) was associated with reduced melanoma‐specific survival (P = 0.0060) in 878 patients with stage I and stage II melanoma (Law et al., ). Observations of such opposite relationships certainly dictate further functional studies to help better understand their biological implications; nevertheless, these studies provide further support that melanoma risk loci may impact melanoma outcomes.…”

Section: Melanoma Risk Genes Associated With Prognosismentioning

confidence: 64%

Germline determinants of clinical outcome of cutaneous melanoma

Vogelsang

Wilson

Kirchhoff

2015

Pigment Cell Melanoma Res

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Cutaneous melanoma (CM) is the most lethal form of skin cancer. Despite the constant increase of melanoma incidence, which is in part due to incremental advances in early diagnostic modalities, mortality rates have not improved over the last decade and for advanced stages remain steadily high. While conventional prognostic biomarkers currently in use find significant utility for predicting overall general survival probabilities, they are not sensitive enough for a more personalized clinical assessment on an individual level. In recent years, the advent of genomic technologies has brought the promise of identification of germline DNA alterations that may associate with CM outcomes and hence represent novel biomarkers for clinical utilization. This review attempts to summarize the current state of knowledge of germline genetic factors studied for their impact on melanoma clinical outcomes. We also discuss ongoing problems and hurdles in validating such surrogates, and we also project future directions in discovery of more powerful germline genetic factors with clinical utility in melanoma prognostication.

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Section: Melanoma Risk Genes Associated With Prognosismentioning

confidence: 64%

Germline determinants of clinical outcome of cutaneous melanoma

Vogelsang

Wilson

Kirchhoff

2015

Pigment Cell Melanoma Res

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“…A rare PARP1 variant [c.1129C>T(p.Pro377Ser)] was carried by the (healthy) grandfather only. Common single‐nucleotide polymorphisms in PARP1 reduce melanoma risk, and inhibition of poly(ADP‐ribose) polymerase 1 (PARP1) disrupts metastatic transformation in melanoma . PARP1 regulates the response of p14 ARF to DNA strand breaks .…”

mentioning

confidence: 64%

Point mutation in p14ARF-specific exon 1β of CDKN2A causing familial melanoma and astrocytoma

McInerney-Leo

Wheeler

Sturm

et al. 2018

British Journal of Dermatology

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DEAR EDITOR, Rarely, melanoma is dominantly inherited, with CDKN2A mutations accounting for > 85% of mutation-positive families. 1 CDKN2A encodes two, nonhomologous proteins, p16 and p14 ARF , with individually unique first exons (1a and 1b, respectively) and alternative reading frames. Over 95% of the CDKN2A mutations in familial melanoma occur in the p16 transcript. 1 We obtained consent from a family with melanoma-astrocytoma, negative for mutations in p16 (Fig. 1) for whole-exome sequencing (WES) (trial registration: HREC/09/QPAH/162). The proband presented aged 18 years with both melanoma and astrocytoma. Her mother presented with melanoma aged 27 years, dying at 28 years. Three maternal uncles and both maternal grandparents were well. The maternal grandfather's brother and first cousin died of melanoma in their twenties.WES was performed on DNA from the proband and maternal grandfather using standard techniques. Data were filtered

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“…10 Studies have reported that specific variants in PARP1 disrupt protein function, which is hypothesized to decrease growth of primary tumors and reduce metastatic transformation in melanoma. 11 Notably, the same PARP1 variant was previously hypothesized to be protective in a familial melanoma CDKN2A pedigree. 12 Common "red hair colour" variants in MC1R are classified as "R" and "r", and are associated with a 1.93-and 1.55-fold melanoma risk respectively.…”

Section: Discussionmentioning

confidence: 88%

“…PARP1 is involved with DNA damage response via DNA damage sensors and signal transducers 10 . Studies have reported that specific variants in PARP1 disrupt protein function, which is hypothesized to decrease growth of primary tumors and reduce metastatic transformation in melanoma 11 . Notably, the same PARP1 variant was previously hypothesized to be protective in a familial melanoma CDKN2A pedigree 12…”

Section: Discussionmentioning

confidence: 96%

Amelanotic/hypopigmented melanoma in a sibship with oculocutaneous albinism

Maas

Wallingford

McGuire

et al. 2022

The Journal of Dermatology

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Oculocutaneous albinism (OCA) comprises a group of heterogeneous disorders characterized by hypopigmentation of the skin, eyes, and hair secondary to decreased/absent melanin. 1 OCA is caused by autosomal recessive variants in genes impacting the melanin biosynthesis (TYR, OCA2, TYRP1, SLC45A2, SLC24A5, and C10orf11 2 ). Clinical subtypes of OCA correlate with degrees of pigmentation (OCA1A, OCA1B, OCA2, OCA3, and OCA4), where the most severe form, OCA1A, is characterized by complete lack of melanin production. 2 Melanin deficiency makes OCA-affected individuals more vulnerable to basal cell and squamous cell carcinomas. 2 Melanomas rarely occur in OCA, accounting for ~1% of skin malignancies. 2 Rarer still is the co-occurrence of multiple primary melanomas (MPM) and OCA. 3 When individuals with OCA develop melanoma, it is typically in the amelanotic/hypopigmented (AHM) form, 3 which is conversely rare in the general population. 4This study describes three siblings with OCA1B where two sisters were diagnosed with primary AHM and their brother had no melanoma history. Filtering whole-exome sequencing (WES) data for variants in OCA and/or melanoma susceptibility genes, we aimed to identify variants segregating with the melanoma phenotype. Three-dimensional (3D) total-body

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PARP1 polymorphisms play opposing roles in melanoma occurrence and survival

Cited by 7 publications

References 9 publications

Germline determinants of clinical outcome of cutaneous melanoma

Germline determinants of clinical outcome of cutaneous melanoma

Point mutation in p14ARF-specific exon 1β of CDKN2A causing familial melanoma and astrocytoma

Amelanotic/hypopigmented melanoma in a sibship with oculocutaneous albinism

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