Genetically heterogeneous and clonally unrelated metastases may arise in patients with cutaneous melanoma

Terrence M. Katona, Timothy D. Jones, Mingsheng Wang, John N. Eble, Steven D. Billings, Liang Cheng

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Melanoma of the skin frequently metastasizes to multiple regional lymph nodes and to distant sites. It is uncertain whether all metastases originate from the same tumor clone or whether the genetic heterogeneity of the primary tumor is reflected in the multiple metastases. A total of 73 archival, formalin-fixed, paraffin-embedded, melanoma lesions, including 13 primary tumors and 60 metastases, were studied from 13 patients each having 2 or more metastatic tumors. Genomic DNA samples were prepared from tissue sections using laser-assisted microdissection. We find that the majority of melanoma metastases share a common clonal origin with the matched primary tumor. However, significant genetic divergence occurs frequently during the clonal evolution of metastatic melanoma. In addition, using X-chromosome inactivation analysis, we find that, in some cases, multiple coexisting metastases seem to be derived from different, genetically unrelated tumor clones, implying that some primary tumors may arise from more than a single transformed melanocyte.

Original languageEnglish (US)
Pages (from-to)1029-1037
Number of pages9
JournalAmerican Journal of Surgical Pathology
Volume31
Issue number7
DOIs
StatePublished - Jul 1 2007

Fingerprint

Melanoma
Neoplasm Metastasis
Skin
Neoplasms
Clone Cells
Clonal Evolution
X Chromosome Inactivation
Microdissection
Genetic Heterogeneity
Melanocytes
Paraffin
Formaldehyde
Lasers
Lymph Nodes
DNA

Keywords

  • Clonality
  • Cutaneous neoplasia
  • Loss of heterozygosity
  • Lymph node metastasis
  • Malignant melanoma
  • Progression
  • Skin
  • X chromosome inactivation

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine

Cite this

Genetically heterogeneous and clonally unrelated metastases may arise in patients with cutaneous melanoma. / Katona, Terrence M.; Jones, Timothy D.; Wang, Mingsheng; Eble, John N.; Billings, Steven D.; Cheng, Liang.

In: American Journal of Surgical Pathology, Vol. 31, No. 7, 01.07.2007, p. 1029-1037.

Research output: Contribution to journalArticle

@article{61c87401bcf3414cb9e4adbcb633fc46,
title = "Genetically heterogeneous and clonally unrelated metastases may arise in patients with cutaneous melanoma",
abstract = "Melanoma of the skin frequently metastasizes to multiple regional lymph nodes and to distant sites. It is uncertain whether all metastases originate from the same tumor clone or whether the genetic heterogeneity of the primary tumor is reflected in the multiple metastases. A total of 73 archival, formalin-fixed, paraffin-embedded, melanoma lesions, including 13 primary tumors and 60 metastases, were studied from 13 patients each having 2 or more metastatic tumors. Genomic DNA samples were prepared from tissue sections using laser-assisted microdissection. We find that the majority of melanoma metastases share a common clonal origin with the matched primary tumor. However, significant genetic divergence occurs frequently during the clonal evolution of metastatic melanoma. In addition, using X-chromosome inactivation analysis, we find that, in some cases, multiple coexisting metastases seem to be derived from different, genetically unrelated tumor clones, implying that some primary tumors may arise from more than a single transformed melanocyte.",
keywords = "Clonality, Cutaneous neoplasia, Loss of heterozygosity, Lymph node metastasis, Malignant melanoma, Progression, Skin, X chromosome inactivation",
author = "Katona, {Terrence M.} and Jones, {Timothy D.} and Mingsheng Wang and Eble, {John N.} and Billings, {Steven D.} and Liang Cheng",
year = "2007",
month = "7",
day = "1",
doi = "10.1097/PAS.0b013e31802b3488",
language = "English (US)",
volume = "31",
pages = "1029--1037",
journal = "American Journal of Surgical Pathology",
issn = "0147-5185",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - Genetically heterogeneous and clonally unrelated metastases may arise in patients with cutaneous melanoma

AU - Katona, Terrence M.

AU - Jones, Timothy D.

AU - Wang, Mingsheng

AU - Eble, John N.

AU - Billings, Steven D.

AU - Cheng, Liang

PY - 2007/7/1

Y1 - 2007/7/1

N2 - Melanoma of the skin frequently metastasizes to multiple regional lymph nodes and to distant sites. It is uncertain whether all metastases originate from the same tumor clone or whether the genetic heterogeneity of the primary tumor is reflected in the multiple metastases. A total of 73 archival, formalin-fixed, paraffin-embedded, melanoma lesions, including 13 primary tumors and 60 metastases, were studied from 13 patients each having 2 or more metastatic tumors. Genomic DNA samples were prepared from tissue sections using laser-assisted microdissection. We find that the majority of melanoma metastases share a common clonal origin with the matched primary tumor. However, significant genetic divergence occurs frequently during the clonal evolution of metastatic melanoma. In addition, using X-chromosome inactivation analysis, we find that, in some cases, multiple coexisting metastases seem to be derived from different, genetically unrelated tumor clones, implying that some primary tumors may arise from more than a single transformed melanocyte.

AB - Melanoma of the skin frequently metastasizes to multiple regional lymph nodes and to distant sites. It is uncertain whether all metastases originate from the same tumor clone or whether the genetic heterogeneity of the primary tumor is reflected in the multiple metastases. A total of 73 archival, formalin-fixed, paraffin-embedded, melanoma lesions, including 13 primary tumors and 60 metastases, were studied from 13 patients each having 2 or more metastatic tumors. Genomic DNA samples were prepared from tissue sections using laser-assisted microdissection. We find that the majority of melanoma metastases share a common clonal origin with the matched primary tumor. However, significant genetic divergence occurs frequently during the clonal evolution of metastatic melanoma. In addition, using X-chromosome inactivation analysis, we find that, in some cases, multiple coexisting metastases seem to be derived from different, genetically unrelated tumor clones, implying that some primary tumors may arise from more than a single transformed melanocyte.

KW - Clonality

KW - Cutaneous neoplasia

KW - Loss of heterozygosity

KW - Lymph node metastasis

KW - Malignant melanoma

KW - Progression

KW - Skin

KW - X chromosome inactivation

UR - http://www.scopus.com/inward/record.url?scp=34347355444&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34347355444&partnerID=8YFLogxK

U2 - 10.1097/PAS.0b013e31802b3488

DO - 10.1097/PAS.0b013e31802b3488

M3 - Article

C2 - 17592269

AN - SCOPUS:34347355444

VL - 31

SP - 1029

EP - 1037

JO - American Journal of Surgical Pathology

JF - American Journal of Surgical Pathology

SN - 0147-5185

IS - 7

ER -