Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families: The familial atypical multiple mole melanoma-pancreatic carcinoma syndrome

Henry T. Lynch, Randall E. Brand, David Hogg, Carolyn A. Deters, Ramon M. Fusaro, Jane F. Lynch, Ling Liu, Joseph Knezetic, Norman J. Lassam, Michael Goggins, Scott Kern

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. Hereditary pancreatic carcinoma shows extant phenotypic and genotypic heterogeneity as evidenced by its integral association with a variety of hereditary cancer syndromes inclusive of the familial atypical multiple mole melanoma (FAMMM) syndrome in concert with CDKN2A (p16) germline mutations. METHODS. Creighton University's familial pancreatic carcinoma resource comprises 159 families of which 19 (12%) show the FAMMM cutaneous phenotypes. The authors describe eight families with the FAMMM-pancreatic carcinoma (FAMMM-PC) association in concert with a CDKN2A germline mutation. Each family was thoroughly educated about all facets of the study, including the molecular genetics, reduced penetrance of CDKN2A mutations, and their variable expressivity. Genetic counseling was provided to each patient. RESULTS. Diversity in cancer presentation within and among the families was noteworthy, wherein melanoma predominated in certain of the families whereas pancreatic carcinoma predominated in others. Early-onset pancreatic carcinoma (at ages 35, 45, 46, and 49 years) appeared in some of the families whereas markedly later-onset pancreatic carcinoma occurred in others. There were four incidences of melanoma and pancreatic carcinoma as double primaries in the same individuals. One patient with melanoma and pancreatic carcinoma had a third primary of breast carcinoma. Another patient had sarcoma, esophageal carcinoma, and two melanoma primaries, whereas his daughter had sarcoma and was a carrier of a CDKN2A mutation. CONCLUSIONS. The authors suggest that these tumors may collectively, in concert with CDKN2A mutations, constitute a "new" putative hereditary carcinoma syndrome referred to as FAMMM-PC. More clinical and molecular genetic research on additional families with pancreatic carcinoma in concert with the FAMMM will be required.

Original languageEnglish
Pages (from-to)84-96
Number of pages13
JournalCancer
Volume94
Issue number1
DOIs
StatePublished - Jan 1 2002

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Dysplastic Nevus Syndrome
Germ-Line Mutation
Melanoma
Sarcoma
Mutation
Molecular Biology
Hereditary Neoplastic Syndromes
Carcinoma
Genetic Research
Pancreatic Carcinoma
Melanoma-Pancreatic Cancer Syndrome
Penetrance
Genetic Counseling
Nuclear Family
Neoplasms
Breast Neoplasms
Phenotype
Skin

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

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Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families : The familial atypical multiple mole melanoma-pancreatic carcinoma syndrome. / Lynch, Henry T.; Brand, Randall E.; Hogg, David; Deters, Carolyn A.; Fusaro, Ramon M.; Lynch, Jane F.; Liu, Ling; Knezetic, Joseph; Lassam, Norman J.; Goggins, Michael; Kern, Scott.

In: Cancer, Vol. 94, No. 1, 01.01.2002, p. 84-96.

Research output: Contribution to journalArticle

Lynch, Henry T. ; Brand, Randall E. ; Hogg, David ; Deters, Carolyn A. ; Fusaro, Ramon M. ; Lynch, Jane F. ; Liu, Ling ; Knezetic, Joseph ; Lassam, Norman J. ; Goggins, Michael ; Kern, Scott. / Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families : The familial atypical multiple mole melanoma-pancreatic carcinoma syndrome. In: Cancer. 2002 ; Vol. 94, No. 1. pp. 84-96.
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abstract = "BACKGROUND. Hereditary pancreatic carcinoma shows extant phenotypic and genotypic heterogeneity as evidenced by its integral association with a variety of hereditary cancer syndromes inclusive of the familial atypical multiple mole melanoma (FAMMM) syndrome in concert with CDKN2A (p16) germline mutations. METHODS. Creighton University's familial pancreatic carcinoma resource comprises 159 families of which 19 (12{\%}) show the FAMMM cutaneous phenotypes. The authors describe eight families with the FAMMM-pancreatic carcinoma (FAMMM-PC) association in concert with a CDKN2A germline mutation. Each family was thoroughly educated about all facets of the study, including the molecular genetics, reduced penetrance of CDKN2A mutations, and their variable expressivity. Genetic counseling was provided to each patient. RESULTS. Diversity in cancer presentation within and among the families was noteworthy, wherein melanoma predominated in certain of the families whereas pancreatic carcinoma predominated in others. Early-onset pancreatic carcinoma (at ages 35, 45, 46, and 49 years) appeared in some of the families whereas markedly later-onset pancreatic carcinoma occurred in others. There were four incidences of melanoma and pancreatic carcinoma as double primaries in the same individuals. One patient with melanoma and pancreatic carcinoma had a third primary of breast carcinoma. Another patient had sarcoma, esophageal carcinoma, and two melanoma primaries, whereas his daughter had sarcoma and was a carrier of a CDKN2A mutation. CONCLUSIONS. The authors suggest that these tumors may collectively, in concert with CDKN2A mutations, constitute a {"}new{"} putative hereditary carcinoma syndrome referred to as FAMMM-PC. More clinical and molecular genetic research on additional families with pancreatic carcinoma in concert with the FAMMM will be required.",
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T1 - Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families

T2 - The familial atypical multiple mole melanoma-pancreatic carcinoma syndrome

AU - Lynch, Henry T.

AU - Brand, Randall E.

AU - Hogg, David

AU - Deters, Carolyn A.

AU - Fusaro, Ramon M.

AU - Lynch, Jane F.

AU - Liu, Ling

AU - Knezetic, Joseph

AU - Lassam, Norman J.

AU - Goggins, Michael

AU - Kern, Scott

PY - 2002/1/1

Y1 - 2002/1/1

N2 - BACKGROUND. Hereditary pancreatic carcinoma shows extant phenotypic and genotypic heterogeneity as evidenced by its integral association with a variety of hereditary cancer syndromes inclusive of the familial atypical multiple mole melanoma (FAMMM) syndrome in concert with CDKN2A (p16) germline mutations. METHODS. Creighton University's familial pancreatic carcinoma resource comprises 159 families of which 19 (12%) show the FAMMM cutaneous phenotypes. The authors describe eight families with the FAMMM-pancreatic carcinoma (FAMMM-PC) association in concert with a CDKN2A germline mutation. Each family was thoroughly educated about all facets of the study, including the molecular genetics, reduced penetrance of CDKN2A mutations, and their variable expressivity. Genetic counseling was provided to each patient. RESULTS. Diversity in cancer presentation within and among the families was noteworthy, wherein melanoma predominated in certain of the families whereas pancreatic carcinoma predominated in others. Early-onset pancreatic carcinoma (at ages 35, 45, 46, and 49 years) appeared in some of the families whereas markedly later-onset pancreatic carcinoma occurred in others. There were four incidences of melanoma and pancreatic carcinoma as double primaries in the same individuals. One patient with melanoma and pancreatic carcinoma had a third primary of breast carcinoma. Another patient had sarcoma, esophageal carcinoma, and two melanoma primaries, whereas his daughter had sarcoma and was a carrier of a CDKN2A mutation. CONCLUSIONS. The authors suggest that these tumors may collectively, in concert with CDKN2A mutations, constitute a "new" putative hereditary carcinoma syndrome referred to as FAMMM-PC. More clinical and molecular genetic research on additional families with pancreatic carcinoma in concert with the FAMMM will be required.

AB - BACKGROUND. Hereditary pancreatic carcinoma shows extant phenotypic and genotypic heterogeneity as evidenced by its integral association with a variety of hereditary cancer syndromes inclusive of the familial atypical multiple mole melanoma (FAMMM) syndrome in concert with CDKN2A (p16) germline mutations. METHODS. Creighton University's familial pancreatic carcinoma resource comprises 159 families of which 19 (12%) show the FAMMM cutaneous phenotypes. The authors describe eight families with the FAMMM-pancreatic carcinoma (FAMMM-PC) association in concert with a CDKN2A germline mutation. Each family was thoroughly educated about all facets of the study, including the molecular genetics, reduced penetrance of CDKN2A mutations, and their variable expressivity. Genetic counseling was provided to each patient. RESULTS. Diversity in cancer presentation within and among the families was noteworthy, wherein melanoma predominated in certain of the families whereas pancreatic carcinoma predominated in others. Early-onset pancreatic carcinoma (at ages 35, 45, 46, and 49 years) appeared in some of the families whereas markedly later-onset pancreatic carcinoma occurred in others. There were four incidences of melanoma and pancreatic carcinoma as double primaries in the same individuals. One patient with melanoma and pancreatic carcinoma had a third primary of breast carcinoma. Another patient had sarcoma, esophageal carcinoma, and two melanoma primaries, whereas his daughter had sarcoma and was a carrier of a CDKN2A mutation. CONCLUSIONS. The authors suggest that these tumors may collectively, in concert with CDKN2A mutations, constitute a "new" putative hereditary carcinoma syndrome referred to as FAMMM-PC. More clinical and molecular genetic research on additional families with pancreatic carcinoma in concert with the FAMMM will be required.

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