Histologic features of melanoma associated with germline mutations of CDKN2A, CDK4, and POT1 in melanoma-prone families from the United States, Italy, and Spain
CDKN2A, CDK4, and POT1 are well-established melanoma-susceptibility genes. We evaluated melanoma histopathology for individuals with germline mutations of CDKN2A, CDK4, and POT1. We assessed histopathology for melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) from the Uni...
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| Veröffentlicht in: | Journal of the American Academy of Dermatology 2020-09, Vol.83 (3), p.860-869 |
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| creator | Sargen, Michael R. Calista, Donato Elder, David E. Massi, Daniela Chu, Emily Y. Potrony, Míriam Pfeiffer, Ruth M. Carrera, Cristina Aguilera, Paula Alos, Llucia Puig, Susana Elenitsas, Rosalie Yang, Xiaohong R. Tucker, Margaret A. Landi, Maria Teresa Goldstein, Alisa M. |
| description | CDKN2A, CDK4, and POT1 are well-established melanoma-susceptibility genes.
We evaluated melanoma histopathology for individuals with germline mutations of CDKN2A, CDK4, and POT1.
We assessed histopathology for melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) from the United States, Italy, and Spain. Comparisons between mutation carriers and noncarriers (no mutation) were adjusted for age, sex, Breslow depth, and correlations among individuals within the same family.
Histologic slides were evaluated for 290 melanomas (139 from 132 noncarriers, 122 from 68 CDKN2A carriers, 10 from 6 CDK4 carriers, and 19 from 16 POT1 carriers). Superficial spreading was the predominant subtype for all groups. Spitzoid morphology (>25% of tumor) was observed in 10 of 15 invasive melanomas (67%) from POT1 carriers (P |
| doi_str_mv | 10.1016/j.jaad.2020.03.100 |
| format | Article |
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We evaluated melanoma histopathology for individuals with germline mutations of CDKN2A, CDK4, and POT1.
We assessed histopathology for melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) from the United States, Italy, and Spain. Comparisons between mutation carriers and noncarriers (no mutation) were adjusted for age, sex, Breslow depth, and correlations among individuals within the same family.
Histologic slides were evaluated for 290 melanomas (139 from 132 noncarriers, 122 from 68 CDKN2A carriers, 10 from 6 CDK4 carriers, and 19 from 16 POT1 carriers). Superficial spreading was the predominant subtype for all groups. Spitzoid morphology (>25% of tumor) was observed in 10 of 15 invasive melanomas (67%) from POT1 carriers (P < .0001 vs noncarriers). This finding was independently confirmed by 3 expert melanoma dermatopathologists in 9 of 15 invasive melanomas (60%). In situ and invasive melanomas from CDKN2A and CDK4 carriers were histologically similar to melanomas from noncarriers.
Limited sample sizes for rare melanoma-susceptibility syndromes (CDK4, POT1).
Spitzoid morphology was associated with POT1 mutations suggesting that telomere dysfunction (POT1 mutations) may contribute to spitzoid differentiation in melanocytic tumors.</description><identifier>ISSN: 0190-9622</identifier><identifier>EISSN: 1097-6787</identifier><identifier>DOI: 10.1016/j.jaad.2020.03.100</identifier><identifier>PMID: 32283231</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; CDK4 ; CDKN2A ; Cyclin-Dependent Kinase 4 - genetics ; Cyclin-Dependent Kinase Inhibitor p16 - genetics ; familial melanoma ; Female ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Heterozygote ; Humans ; Italy ; Male ; melanoma ; Melanoma - genetics ; Melanoma - pathology ; melanoma-prone families ; melanoma-susceptibility genes ; Middle Aged ; Neoplasm Invasiveness - genetics ; POT1 ; Skin - pathology ; Skin Neoplasms - genetics ; Skin Neoplasms - pathology ; Spain ; Spitz ; spitzoid ; Telomere-Binding Proteins - genetics ; tumor infiltrating lymphocytes ; United States</subject><ispartof>Journal of the American Academy of Dermatology, 2020-09, Vol.83 (3), p.860-869</ispartof><rights>2020</rights><rights>Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-d0b382111fc949fb1ff7cf0de7c89cb5d273923d2f0b774e5771cd8aab5fadd33</citedby><cites>FETCH-LOGICAL-c455t-d0b382111fc949fb1ff7cf0de7c89cb5d273923d2f0b774e5771cd8aab5fadd33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0190962220305235$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32283231$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sargen, Michael R.</creatorcontrib><creatorcontrib>Calista, Donato</creatorcontrib><creatorcontrib>Elder, David E.</creatorcontrib><creatorcontrib>Massi, Daniela</creatorcontrib><creatorcontrib>Chu, Emily Y.</creatorcontrib><creatorcontrib>Potrony, Míriam</creatorcontrib><creatorcontrib>Pfeiffer, Ruth M.</creatorcontrib><creatorcontrib>Carrera, Cristina</creatorcontrib><creatorcontrib>Aguilera, Paula</creatorcontrib><creatorcontrib>Alos, Llucia</creatorcontrib><creatorcontrib>Puig, Susana</creatorcontrib><creatorcontrib>Elenitsas, Rosalie</creatorcontrib><creatorcontrib>Yang, Xiaohong R.</creatorcontrib><creatorcontrib>Tucker, Margaret A.</creatorcontrib><creatorcontrib>Landi, Maria Teresa</creatorcontrib><creatorcontrib>Goldstein, Alisa M.</creatorcontrib><title>Histologic features of melanoma associated with germline mutations of CDKN2A, CDK4, and POT1 in melanoma-prone families from the United States, Italy, and Spain</title><title>Journal of the American Academy of Dermatology</title><addtitle>J Am Acad Dermatol</addtitle><description>CDKN2A, CDK4, and POT1 are well-established melanoma-susceptibility genes.
We evaluated melanoma histopathology for individuals with germline mutations of CDKN2A, CDK4, and POT1.
We assessed histopathology for melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) from the United States, Italy, and Spain. Comparisons between mutation carriers and noncarriers (no mutation) were adjusted for age, sex, Breslow depth, and correlations among individuals within the same family.
Histologic slides were evaluated for 290 melanomas (139 from 132 noncarriers, 122 from 68 CDKN2A carriers, 10 from 6 CDK4 carriers, and 19 from 16 POT1 carriers). Superficial spreading was the predominant subtype for all groups. Spitzoid morphology (>25% of tumor) was observed in 10 of 15 invasive melanomas (67%) from POT1 carriers (P < .0001 vs noncarriers). This finding was independently confirmed by 3 expert melanoma dermatopathologists in 9 of 15 invasive melanomas (60%). In situ and invasive melanomas from CDKN2A and CDK4 carriers were histologically similar to melanomas from noncarriers.
Limited sample sizes for rare melanoma-susceptibility syndromes (CDK4, POT1).
Spitzoid morphology was associated with POT1 mutations suggesting that telomere dysfunction (POT1 mutations) may contribute to spitzoid differentiation in melanocytic tumors.</description><subject>Adult</subject><subject>CDK4</subject><subject>CDKN2A</subject><subject>Cyclin-Dependent Kinase 4 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - genetics</subject><subject>familial melanoma</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Germ-Line Mutation</subject><subject>Heterozygote</subject><subject>Humans</subject><subject>Italy</subject><subject>Male</subject><subject>melanoma</subject><subject>Melanoma - genetics</subject><subject>Melanoma - pathology</subject><subject>melanoma-prone families</subject><subject>melanoma-susceptibility genes</subject><subject>Middle Aged</subject><subject>Neoplasm Invasiveness - genetics</subject><subject>POT1</subject><subject>Skin - pathology</subject><subject>Skin Neoplasms - genetics</subject><subject>Skin Neoplasms - pathology</subject><subject>Spain</subject><subject>Spitz</subject><subject>spitzoid</subject><subject>Telomere-Binding Proteins - genetics</subject><subject>tumor infiltrating lymphocytes</subject><subject>United States</subject><issn>0190-9622</issn><issn>1097-6787</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9uEzEQxi0EoqHwAhyQjxyyYWxn410JIVXhTysqitT2bHntceJod53a3qK-DY_KLikRXDiNNPN9v7HnI-Q1gwUDtnq3W-y0tgsOHBYgxh48ITMGtSxWspJPyQxYDUW94vyEvEhpBwD1Usjn5ERwXgku2Iz8PPcphzZsvKEOdR4iJhoc7bDVfeg01SkF43VGS3_4vKUbjF3re6TdkHX2of8tX3_8-o2fzae6nFPdW_r96oZR3x9BxT6G0eV051s_7nAxdDRvkd72foJfjzRMc3qRdftwQFzvte9fkmdOtwlfPdZTcvv50836vLi8-nKxPrsszLIsc2GhERVnjDlTL2vXMOekcWBRmqo2TWm5FDUXljtopFxiKSUzttK6KZ22VohT8uHA3Q9Nh9Zgn6Nu1T76TscHFbRX_056v1WbcK9kCSUTE-DtIyCGuwFTVp1PBtvx-xiGpLioaslAQDlK-UFqYkgpojuuYaCmaNVOTdGqKVoFYuzBaHrz9wOPlj9ZjoL3BwGOZ7r3GFUyHnuD1kc0Wdng_8f_BTk5t2M</recordid><startdate>20200901</startdate><enddate>20200901</enddate><creator>Sargen, Michael R.</creator><creator>Calista, Donato</creator><creator>Elder, David E.</creator><creator>Massi, Daniela</creator><creator>Chu, Emily Y.</creator><creator>Potrony, Míriam</creator><creator>Pfeiffer, Ruth M.</creator><creator>Carrera, Cristina</creator><creator>Aguilera, Paula</creator><creator>Alos, Llucia</creator><creator>Puig, Susana</creator><creator>Elenitsas, Rosalie</creator><creator>Yang, Xiaohong R.</creator><creator>Tucker, Margaret A.</creator><creator>Landi, Maria Teresa</creator><creator>Goldstein, Alisa M.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200901</creationdate><title>Histologic features of melanoma associated with germline mutations of CDKN2A, CDK4, and POT1 in melanoma-prone families from the United States, Italy, and Spain</title><author>Sargen, Michael R. ; Calista, Donato ; Elder, David E. ; Massi, Daniela ; Chu, Emily Y. ; Potrony, Míriam ; Pfeiffer, Ruth M. ; Carrera, Cristina ; Aguilera, Paula ; Alos, Llucia ; Puig, Susana ; Elenitsas, Rosalie ; Yang, Xiaohong R. ; Tucker, Margaret A. ; Landi, Maria Teresa ; Goldstein, Alisa M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-d0b382111fc949fb1ff7cf0de7c89cb5d273923d2f0b774e5771cd8aab5fadd33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>CDK4</topic><topic>CDKN2A</topic><topic>Cyclin-Dependent Kinase 4 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - genetics</topic><topic>familial melanoma</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Germ-Line Mutation</topic><topic>Heterozygote</topic><topic>Humans</topic><topic>Italy</topic><topic>Male</topic><topic>melanoma</topic><topic>Melanoma - genetics</topic><topic>Melanoma - pathology</topic><topic>melanoma-prone families</topic><topic>melanoma-susceptibility genes</topic><topic>Middle Aged</topic><topic>Neoplasm Invasiveness - genetics</topic><topic>POT1</topic><topic>Skin - pathology</topic><topic>Skin Neoplasms - genetics</topic><topic>Skin Neoplasms - pathology</topic><topic>Spain</topic><topic>Spitz</topic><topic>spitzoid</topic><topic>Telomere-Binding Proteins - genetics</topic><topic>tumor infiltrating lymphocytes</topic><topic>United States</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sargen, Michael R.</creatorcontrib><creatorcontrib>Calista, Donato</creatorcontrib><creatorcontrib>Elder, David E.</creatorcontrib><creatorcontrib>Massi, Daniela</creatorcontrib><creatorcontrib>Chu, Emily Y.</creatorcontrib><creatorcontrib>Potrony, Míriam</creatorcontrib><creatorcontrib>Pfeiffer, Ruth M.</creatorcontrib><creatorcontrib>Carrera, Cristina</creatorcontrib><creatorcontrib>Aguilera, Paula</creatorcontrib><creatorcontrib>Alos, Llucia</creatorcontrib><creatorcontrib>Puig, Susana</creatorcontrib><creatorcontrib>Elenitsas, Rosalie</creatorcontrib><creatorcontrib>Yang, Xiaohong R.</creatorcontrib><creatorcontrib>Tucker, Margaret A.</creatorcontrib><creatorcontrib>Landi, Maria Teresa</creatorcontrib><creatorcontrib>Goldstein, Alisa M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the American Academy of Dermatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sargen, Michael R.</au><au>Calista, Donato</au><au>Elder, David E.</au><au>Massi, Daniela</au><au>Chu, Emily Y.</au><au>Potrony, Míriam</au><au>Pfeiffer, Ruth M.</au><au>Carrera, Cristina</au><au>Aguilera, Paula</au><au>Alos, Llucia</au><au>Puig, Susana</au><au>Elenitsas, Rosalie</au><au>Yang, Xiaohong R.</au><au>Tucker, Margaret A.</au><au>Landi, Maria Teresa</au><au>Goldstein, Alisa M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Histologic features of melanoma associated with germline mutations of CDKN2A, CDK4, and POT1 in melanoma-prone families from the United States, Italy, and Spain</atitle><jtitle>Journal of the American Academy of Dermatology</jtitle><addtitle>J Am Acad Dermatol</addtitle><date>2020-09-01</date><risdate>2020</risdate><volume>83</volume><issue>3</issue><spage>860</spage><epage>869</epage><pages>860-869</pages><issn>0190-9622</issn><eissn>1097-6787</eissn><abstract>CDKN2A, CDK4, and POT1 are well-established melanoma-susceptibility genes.
We evaluated melanoma histopathology for individuals with germline mutations of CDKN2A, CDK4, and POT1.
We assessed histopathology for melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) from the United States, Italy, and Spain. Comparisons between mutation carriers and noncarriers (no mutation) were adjusted for age, sex, Breslow depth, and correlations among individuals within the same family.
Histologic slides were evaluated for 290 melanomas (139 from 132 noncarriers, 122 from 68 CDKN2A carriers, 10 from 6 CDK4 carriers, and 19 from 16 POT1 carriers). Superficial spreading was the predominant subtype for all groups. Spitzoid morphology (>25% of tumor) was observed in 10 of 15 invasive melanomas (67%) from POT1 carriers (P < .0001 vs noncarriers). This finding was independently confirmed by 3 expert melanoma dermatopathologists in 9 of 15 invasive melanomas (60%). In situ and invasive melanomas from CDKN2A and CDK4 carriers were histologically similar to melanomas from noncarriers.
Limited sample sizes for rare melanoma-susceptibility syndromes (CDK4, POT1).
Spitzoid morphology was associated with POT1 mutations suggesting that telomere dysfunction (POT1 mutations) may contribute to spitzoid differentiation in melanocytic tumors.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32283231</pmid><doi>10.1016/j.jaad.2020.03.100</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0190-9622 |
| ispartof | Journal of the American Academy of Dermatology, 2020-09, Vol.83 (3), p.860-869 |
| issn | 0190-9622 1097-6787 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult CDK4 CDKN2A Cyclin-Dependent Kinase 4 - genetics Cyclin-Dependent Kinase Inhibitor p16 - genetics familial melanoma Female Genetic Predisposition to Disease Germ-Line Mutation Heterozygote Humans Italy Male melanoma Melanoma - genetics Melanoma - pathology melanoma-prone families melanoma-susceptibility genes Middle Aged Neoplasm Invasiveness - genetics POT1 Skin - pathology Skin Neoplasms - genetics Skin Neoplasms - pathology Spain Spitz spitzoid Telomere-Binding Proteins - genetics tumor infiltrating lymphocytes United States |
| title | Histologic features of melanoma associated with germline mutations of CDKN2A, CDK4, and POT1 in melanoma-prone families from the United States, Italy, and Spain |
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