Hereditary Cancer Syndromes—A Primer on Diagnosis and Management, Part 2: Gastrointestinal Cancer Syndromes

Samadder, N. Jewel; Baffy, Noemi; Giridhar, Karthik V.; Couch, Fergus J.; Riegert–Johnson, Douglas L.

doi:10.1016/j.mayocp.2019.01.042

Cited by 50 publications

(52 citation statements)

References 107 publications

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“…In scrotal EMPD, TP53 and PIK3CA mutations were present in n = 3 and 2 of 5 cases, respectively. In one scrotal EMPD, a pathogenic MUTYH gene mutation (G393D) was found representing a germline variant (MUTYH‐associated polyposis is an autosomal recessive polyposis syndrome caused by bi‐allelic pathogenic germline variants in the MUTYH gene . No other CNV or gene fusions were detected in any of the tested cases.…”

Section: Resultsmentioning

confidence: 96%

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

et al. 2020

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Background Primary Extra‐mammary Paget's disease (EMPD) is a very rare cutaneous adenocarcinoma affecting anogenital or axillary regions. It is characterized by a prolonged course with recurrences and eventually distant metastatic spread for which no specific therapy is known. Methods Eighteen EMPD (13 vulvar and five scrotal) and ten mammary Paget's disease (MPD) cases were comprehensively profiled for gene mutations, fusions and copy number alterations, and for therapy‐relevant protein biomarkers). Results Mutations in TP53 and PIK3CA were the most frequent in both cohorts: 7/15 and 5/15 in EMPD; 1/6 and 4/7 in MPD HER2 gene amplification was detected in 4/18 EMPD (3 vulvar and 1 scrotal case) in contrast to MPD where it was detected in the majority (7/8) of cases. TOP2A gene amplification was seen in 2/12 EMPD and 1/6 MPD, respectively. Similarly, no difference in estrogen receptor expression was seen between the EMPD (4/15) and MPD (3/10). Androgen receptor was also expressed in the majority of both cohorts (12/16 EMPD) and (7/8 MPD).Here ARv7 splice variant was detected in 1/7 EMPD and 1/4 MPD cases, respectively. PD‐L1 expression on immune cells was exclusively observed in three vulvar EMPD. In contrast to MPD, six EMPDs harbored a “high” tumor mutation burden (≥10 mutations/Mb). All tested cases from both cohorts were MSI stable. Conclusions EMPD shares some targetable biomarkers with its mammary counterpart (steroid receptors, PIK3CA signaling pathways, TOP2A amplification). HER2 positivity is notably lower in EMPD while biomarkers to immune checkpoint inhibitors (high TMB and PD‐L1) were observed in some EMPD. Given that no consistent molecular alteration characterizes EMPD, comprehensive theranostic profiling is required to identify individual patients with targetable molecular alterations.

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Section: Resultsmentioning

confidence: 96%

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

et al. 2020

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“…6,7 Genetic susceptibility to CRC includes well-defined inherited syndromes, such as Lynch syndrome, familial adenomatous polyposis (FAP), and MUTYH-associated polyposis (MAP), 2,8 and rare inherited syndromes, including juvenile polyposis syndrome ( JPS), Cowden syndrome/PTEN hamartoma tumor syndrome (PHTS), and Peutz-Jeghers syndrome (PJS). 9,10 Some syndromes are still being further characterized, such as the I1307K polymorphism in APC 11,12 and polymerase proofreading-associated polyposis secondary to germline mutations in POLE and POLD1. 13,14 In addition, there are other syndromes that do not yet have a clearly identified pathogenic variant, such as serrated polyposis syndrome.…”

Section: Overviewmentioning

confidence: 99%

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 2.2019

Gupta

Provenzale

Llor

et al. 2019

Journal of the National Comprehensive Cancer Network

225

177

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Identifying individuals with hereditary syndromes allows for improved cancer surveillance, risk reduction, and optimized management. Establishing criteria for assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the assessment and management of patients with high-risk colorectal cancer syndromes. These NCCN Guidelines Insights focus on criteria for the evaluation of Lynch syndrome and considerations for use of multigene testing in the assessment of hereditary colorectal cancer syndromes.

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“…Hereditary breast ovarian cancer (HBOC) can be defined as a genetic disorder in which breast and ovarian malignant tumors seem to cluster within families . The main factors that suggest a hereditary cancer predisposition syndrome are young age at cancer diagnosis, multiple tumors, bilateral tumors, presence of rare tumors, several cancer‐affected relatives, autosomal dominant inheritance and, in some cases, ethnicity .…”

Section: Introductionmentioning

confidence: 99%

“…Hereditary breast ovarian cancer (HBOC) can be defined as a genetic disorder in which breast and ovarian malignant tumors seem to cluster within families. 1 The main factors that suggest a hereditary cancer predisposition syndrome are young age at cancer diagnosis, multiple tumors, bilateral tumors, presence of rare tumors, several cancer-affected relatives, autosomal dominant inheritance and, in some cases, ethnicity. [2][3][4][5][6][7] Families with these characteristics should be referred to specialized hospital/centers that offer cancer risk assessment and genetic counseling [8][9][10] In Italy, most cancer genetic services are largely distributed in the country but they are not regulated by the national health system rules.…”

Section: Introductionmentioning

confidence: 99%

A regional population‐based hereditary breast cancer screening tool in Italy: First 5‐year results

et al. 2020

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Background Up to 10% of individuals with breast cancer (BC) belong to families with hereditary syndromes. The aim of this study was to develop an instrument to identify individuals/families at high‐hereditary risk for BC and offer dedicated surveillance programs according to different risks. Methods The instrument consisted of a primary questionnaire collecting history of BC and ovarian cancer (OC). This questionnaire was applied to women enrolled in the Emilia‐Romagna Breast Cancer Screening Program. General practitioners (GPs) and specialists could propose the same questionnaire too. Women with a score of ≥ 2, were invited to complete an oncogenetic counseling. According to the Tyrer‐Cuzick evaluation, women considered at high risk were invited to involve the most representative alive individual of the family affected with BC/OC for BRCA1/2 genetic testing. Results Since January 2012 and December 2016, 660 040 women were evaluated by the regional screening program, of which 22 289 (3.5%) were invited to the Spoke evaluation, but only 5615 accepted (25.2%). Totally, also considering women sent by GPs and specialists, 11 667 were assessed and 5554 were sent to the Hub evaluation. Finally, 2342 (42.8%) women fulfilled the criteria for genetic testing, and 544 (23.2%) resulted BRCA1/2 mutation carriers. Conclusions To our knowledge, this is the first regional population‐based multistep model that is aimed to identify individuals with BRCA1/2 mutations and to offer an intensive surveillance program for hereditary‐high risk women. This tool is feasible and effective, even if more efforts must be performed to increase the acceptance of multiple assessments by the study population.

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Hereditary Cancer Syndromes—A Primer on Diagnosis and Management, Part 2: Gastrointestinal Cancer Syndromes

Cited by 50 publications

References 107 publications

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 2.2019

A regional population‐based hereditary breast cancer screening tool in Italy: First 5‐year results

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