RESUMO
We addressed uncertainties regarding hereditary leiomyomatosis and renal cell carcinoma (HLRCC) by exploring all French cases, representing the largest series to date. Fumarate hydratase (FH) germline testing was performed with Sanger sequencing and qPCR/MLPA. Enzyme activity was measured when necessary. We carried out whenever possible a pathology review of RCC and S-(2-succino)-cysteine (2SC)/fumarate hydratase immunohistochemistry. We estimated survival using non-parametric Kaplan-Meier. There were 182 cases from 114 families. Thirty-seven RCC were diagnosed in 34 carriers (19%) at a median age of 40. Among the 23 RCC with pathology review, 13 were papillary type 2. There were 4 papillary RCC of unspecified type, 3 unclassified, 2 tubulocystic, and 1 collecting duct (CD) RCC, all 2SC+ and most (8/10) FH-. Of the remaining 14, papillary type 2, papillary unspecified, CD, and clear cell histologies were reported. The vast majority of RCC (82%) were metastatic at diagnosis or rapidly became metastatic. Median survival for metastatic disease was 18 months (95%CI: 11-29). 133 cases (73%) had a history of cutaneous leiomyomas, 3 developed skin leiomyosarcoma. Uterine leiomyomas were frequent in women (77%), but no sarcomas were observed. Only 2 cases had pheochromocytomas/paraganglioma. CONCLUSION: Our findings have direct implications regarding the identification and management of HLRCC patients.
Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Carcinoma de Células Renais/genética , Fumarato Hidratase/genética , Leiomiomatose/genética , Leiomiossarcoma/genética , Síndromes Neoplásicas Hereditárias/genética , Feocromocitoma/genética , Neoplasias Cutâneas/genética , Neoplasias Uterinas/genética , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Criança , Feminino , França , Expressão Gênica , Predisposição Genética para Doença , Heterozigoto , Humanos , Leiomiomatose/diagnóstico , Leiomiomatose/mortalidade , Leiomiomatose/patologia , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/mortalidade , Leiomiossarcoma/patologia , Metástase Linfática , Pessoa de Meia-Idade , Mutação , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/mortalidade , Síndromes Neoplásicas Hereditárias/patologia , Feocromocitoma/diagnóstico , Feocromocitoma/mortalidade , Feocromocitoma/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologiaRESUMO
Lynch syndrome is an autosomal dominant disease associated with an important risk of cancer, mainly endometrial and colorectal-cancer. This risk can be efficiently lessen by an appropriate screening as far as the mutations carriers are identified. As current clinicopathological recommendations lack sensitivity, a systematic pre-screening of every patient with a colorectal or endometrial cancer can be proposed. Oncogenetic units of the HUG in Geneva and ICHV in Valais have set up a population-based study to evaluate the efficacy of such a strategy. Whatever the approach, the pathologist is directly implicated as Lynch syndrome harbors specific histological aspects that can help to its identification, but also as pre-screening tests are directly realized on tumor-tissue.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias/genética , Neoplasias/prevenção & controle , Predisposição Genética para Doença , HumanosAssuntos
Neoplasias Encefálicas , Neoplasias Colorretais , Reparo de Erro de Pareamento de DNA/genética , Síndromes Neoplásicas Hereditárias , Adolescente , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Criança , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , DNA Polimerase II/genética , DNA Polimerase III/genética , Diagnóstico Diferencial , Aconselhamento Genético , Mutação em Linhagem Germinativa , Guias como Assunto , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Síndrome de Li-Fraumeni/psicologia , Lúpus Eritematoso Sistêmico/genética , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/terapia , Países Baixos , Proteínas de Ligação a Poli-ADP-Ribose/genética , Vacinação , Adulto JovemRESUMO
ERBB2 is frequently amplified in breast tumours as part of a wide region of amplification on chromosome 17q21. This amplicon contains many candidate genes for breast cancer susceptibility. We used a genetic association study design to determine if common genetic variation (frequency>or=5%) in a 400-kb region surrounding ERBB2 and containing the PPARBP, CRK7, NEUROD2, PPP1R1B, STARD3, TCAP, PNMT, CAB2, ERBB2, C17ORF37, GRB7 and ZNFN1A3 genes, was associated with breast cancer risk. Sixteen tagging single-nucleotide polymorphisms (tSNPs) selected within blocks of linkage disequilibrium from the HapMap database, one HapMap singleton SNP, and six additional SNPs randomly selected from dbSNP were genotyped using Taqman in a large study set of British women (2275 cases, 2280 controls). We observed no association between any of the genotypes or associated haplotypes and disease risk. In order to simulate unidentified SNPs, we performed the leave-one-out cross-validation procedure on the HapMap data; over 90% of the common genetic variation was well represented by tagging polymorphisms. We are therefore likely to have tagged any common variants present in our population. In summary, we found no association between common genetic variation in the 17q21 ERBB2 amplicon and breast cancer risk in British women.