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Tumor genetic heterogeneity analysis of chronic sun-damaged melanoma

Sanna, Adriana LU ; Harbst, Katja LU ; Johansson, Iva LU ; Christensen, Gustav LU ; Lauss, Martin LU ; Mitra, Shamik LU ; Rosengren, Frida LU ; Häkkinen, Jari LU ; Vallon-Christersson, Johan LU and Olsson, Håkan LU , et al. (2019) In Pigment Cell & Melanoma Research
Abstract

Chronic sun-damaged (CSD) melanoma represents 10%-20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra-deep targeted sequencing of 40 cancer-associated genes was performed in 72 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole exome and RNA sequencing on multiple regions of primary tumor and multiple in-transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma-related genes or in mutational load between in situ and invasive CSDhigh lesions, while this... (More)

Chronic sun-damaged (CSD) melanoma represents 10%-20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra-deep targeted sequencing of 40 cancer-associated genes was performed in 72 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole exome and RNA sequencing on multiple regions of primary tumor and multiple in-transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma-related genes or in mutational load between in situ and invasive CSDhigh lesions, while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1, and TP53 mutations (p < .01, Fisher's exact test) was found in CSDhigh melanomas. Sequencing of multiple specimens from one CSDhigh patient revealed strikingly limited ITH with >95% shared mutations. Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes.

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Pigment Cell & Melanoma Research
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Wiley-Blackwell
external identifiers
  • pmid:31811783
  • scopus:85076934297
ISSN
1755-148X
DOI
10.1111/pcmr.12851
language
English
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yes
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© 2019 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.
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c94ded92-04be-4181-80c1-f13a7f07a88b
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2020-01-10 12:55:14
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2020-02-01 02:21:02
@article{c94ded92-04be-4181-80c1-f13a7f07a88b,
  abstract     = {<p>Chronic sun-damaged (CSD) melanoma represents 10%-20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra-deep targeted sequencing of 40 cancer-associated genes was performed in 72 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole exome and RNA sequencing on multiple regions of primary tumor and multiple in-transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma-related genes or in mutational load between in situ and invasive CSDhigh lesions, while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1, and TP53 mutations (p &lt; .01, Fisher's exact test) was found in CSDhigh melanomas. Sequencing of multiple specimens from one CSDhigh patient revealed strikingly limited ITH with &gt;95% shared mutations. Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes.</p>},
  author       = {Sanna, Adriana and Harbst, Katja and Johansson, Iva and Christensen, Gustav and Lauss, Martin and Mitra, Shamik and Rosengren, Frida and Häkkinen, Jari and Vallon-Christersson, Johan and Olsson, Håkan and Ingvar, Åsa and Isaksson, Karolin and Ingvar, Christian and Nielsen, Kari and Jönsson, Göran},
  issn         = {1755-148X},
  language     = {eng},
  month        = {12},
  publisher    = {Wiley-Blackwell},
  series       = {Pigment Cell & Melanoma Research},
  title        = {Tumor genetic heterogeneity analysis of chronic sun-damaged melanoma},
  url          = {http://dx.doi.org/10.1111/pcmr.12851},
  doi          = {10.1111/pcmr.12851},
  year         = {2019},
}