Low likelihood that potential germline findings identified during somatic tumor testing are evaluated: Room for improvement.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13037-e13037
Author(s):  
Heather Wright ◽  
Cuke Melissa ◽  
Edmund Folefac ◽  
Claire F. Verschraegen ◽  
Marie Wood
Keyword(s):  
Genetic Counseling ◽  
Hereditary Cancer ◽  
Retrospective Chart Review ◽  
Germline Mutations ◽  
Cancer Center ◽  
Genomic Testing ◽  
Opportunity Identification ◽  
History Of ◽  
Record Review ◽  
Germline Testing

e13037 Background: Genomic testing, useful for treatment planning, may indicate the presence of a germline mutation. We evaluate the incidence of potentially actionable germline mutations detected via genomic testing and determined rates of follow-up referrals for genetic counseling and germline testing among patients with potential germline mutations. Methods: This was a retrospective chart review of patients who underwent genomic testing at The University of Vermont Cancer Center (UVMCC). Test reports were reviewed for mutations in 24 genes associated with hereditary cancer and recognized as clinically actionable by the American College of Medical Genetics. Medical record review was performed to identify patients referred for genetic counseling and results of germline testing. Results: Between 8/2009 and 9/2016 157 patients underwent genomic testing at UVMCC. Eighty-one percent (127/157) had a mutation in ≥ 1 gene associated with hereditary cancer (range 0-4 mutations per patient), and 46% (73/157) had mutations in more than one gene. Potential germline mutations were most commonly identified in TP53, CDKN2A, RB1, PTEN, STK11 and APC (each with mutations in > 10% of patients). To date only 12% (15/127) of patients with potential germline mutations have been referred for genetic counseling. Two were referred for evaluation of findings seen on genomic testing others being referred for personal or family history of cancer. The majority (11/15) of referred patients have undergone genetic testing with 27% (3/11) having germline mutations identified; 2/3 of which were also identified on genomic testing. Conclusions: Genomic testing can be an important tool for identifying hereditary cancer syndromes. While the majority (81%) of patient’s undergoing genomic testing had mutations genes associated with hereditary cancer, the low rate of referral (12%) for genetic counseling to determine if these are truly germline represents a significant missed opportunity. Identification of germline mutations has implications for both the patient (for treatment and risk of second cancers) and their family. Patients and their providers should be aware of the potential for germline findings when genomic testing is performed.

Potential germline findings identified during somatic tumor testing: Room for improvement.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1543-1543
Author(s):  
Sundas Khan ◽  
Heather Wright ◽  
Melissa Cuke ◽  
Edmund Folefac ◽  
Claire F. Verschraegen ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Germline Mutation ◽  
Hereditary Cancer ◽  
Germline Mutations ◽  
Cancer Center ◽  
Genomic Testing ◽  
Test Results ◽  
Genomic Test ◽  
Tumor Types ◽  
Germline Testing

1543 Background: Genomic testing, useful for treatment planning and identification of patients for clinical trials, may indicate the presence of a germline mutation. We sought to evaluate the incidence of potentially actionable germline mutations detected via genomic testing and determined rates of germline testing among patients with potential germline mutations. Methods: This was a retrospective review of patients undergoing genomic testing at The University of Vermont Cancer Center (UVMCC) between 03/02-11/19. Testing was reviewed for mutations in 60 genes associated with hereditary cancer and recognized as clinically actionable by the American College of Medical Genetics. Records were reviewed for clinical follow-up. Positive (pathogenic or likely pathogenic) genomic test results were evaluated with descriptive analyses. Proportions with 95% confidence intervals are presented and comparisons made using a χ2 test. Results: 342 patients underwent genomic testing at UVMCC over the study period, with a median age of 61. Common tumor types include: CNS (19%), NSCLCA (17%), ovarian (8%), and sarcoma (7%). 59% (203/342) had a mutation in ≥ 1 gene associated with hereditary cancer. Most common tumor types with potential germline mutations include: NSCLCA (25%), CNS (18%), ovarian (8%), sarcoma (8%), and endometrial (7%). Potential germline mutations were most commonly identified in TP53, CDKN2A, PTEN, and RB1 (each with mutations in >6% of patients). 58 patients in the cohort have undergone germline testing, of which 19% were positive for germline mutations. Of patients with mutations in the highly penetrant BRCA, PALB2, and Lynch genes, 71% were positive for germline mutations. Young age ( < 50) did not enrich for germline mutations (p > 0.05). Only 18% (36/203) of patients with potential germline results were referred for genetic counseling. Conclusions: Genomic testing can reveal hereditary cancer syndromes. While the majority of patients with tumor mutations in genes associated with hereditary cancer will not have germline mutations, genetic testing is the only way to confirm this. 19% of patients who underwent genetic testing in this cohort had a pathogenic germline mutation. This was enriched to 71% when considering genes rarely mutated in tumors (BRCA, PALB2, and Lynch genes). Only 17% of this cohort underwent genetic testing, representing a significant missed opportunity given the implications of these findings for both patients and families. Patients and their providers should be aware of the potential for germline findings when genomic testing is performed.

Genetic counseling referrals after next generation sequencing testing.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1515-1515
Author(s):  
Rafael Gonzalez ◽  
Emma Ryan ◽  
Catherine Watson ◽  
Gloria Broadwater ◽  
Noah D. Kauff ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Next Generation Sequencing ◽  
Hereditary Cancer ◽  
Germline Mutations ◽  
Tumor Board ◽  
Hereditary Cancer Syndrome ◽  
Next Generation ◽  
Cancer Syndrome ◽  
Generation Sequencing ◽  
Germline Testing

1515 Background: Next generation sequencing (NGS) testing of tumor tissue or blood is performed to identify ‘actionable’ mutations that might guide patient care. NGS testing might incidentally identify germline mutations associated with cancer syndromes. No distinction is made between germline and somatic alterations on NGS reports, thus confirmatory germline testing is required. In this quality improvement (QI) initiative, we evaluated the frequency of referrals to genetic counseling (GC) for patients with potentially heritable germline mutations identified through NGS testing. Methods: We generated a list of high-risk mutations (HRMs) which merit GC referral based on NCCN guidelines. NGS test results for 3,400 consecutive patients with solid tumor malignancies were reviewed by the molecular tumor board from 1/2014-9/2019 and were screened for pathogenic HRMs. Basic demographic, oncologic, and GC data were retrospectively abstracted for each patient. The outcomes of interest were the frequency of HRMs identified through NGS testing, the proportion of patients subsequently referred to GC, and the proportion of patients ultimately diagnosed with a hereditary cancer syndrome. Results: 472 individual patients (14%) had NGS testing with one or more HRM identified; 465 patients were evaluable which corresponded to 519 HRMs that were included in the analysis (Table). Malignancies included were gastrointestinal 199 (42.8%), lung 83 (17.8%), genitourinary/renal 56 (12.0%), breast 49 (10.5%), gynecologic 35 (7.5%), and other 43 (9.2%). 75 (16.1%) patients had germline testing prior to NGS testing. Of those patients without prior germline genetic testing, 62 (15.9%) were referred to GC, and 19 (4.9%) patients were diagnosed with a hereditary cancer syndrome. Conclusions: Tumor NGS testing identifies HRMs that may represent an undiagnosed heritable germline mutation. Providers ordering NGS tests should review results for HRMs, refer to GC when appropriate, and offer confirmatory germline testing for patients and their families. [Table: see text]

Landscape of germline mutations in 1144 patients (Pts) with gastrointestinal (GI) cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13660-e13660
Author(s):  
Mohamed E. Salem ◽  
Lisa Amacker-North ◽  
Mariah Gleason ◽  
Aly Athens ◽  
William Mills Worrilow ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Hereditary Cancer ◽  
Cancer Susceptibility ◽  
Checkpoint Inhibitors ◽  
Susceptibility Gene ◽  
Germline Mutations ◽  
Gene Panel ◽  
Variant Of Uncertain Significance ◽  
Gi Cancer ◽  
Germline Testing

e13660 Background: The efficacy of PARP inhibitors in germline BRCA-mutated pancreatic adenocarcinoma (PC) and immune checkpoint inhibitors in dMMR colorectal cancer (CRC) shows the importance of genetic testing. We aimed to characterize the frequency of pathogenic/likely pathogenic germline variants (PLPVs) in GI cancer pts. Methods: A retrospective review of pts referred to the Levine Cancer Institute Genetics Program was conducted. Genetic testing used a focused hereditary cancer 4-43 gene panel or pan-cancer 82-84 gene panel. Results: Out of 1144 GI cancer pts seen between 2010 and 2019, 869 underwent germline testing, and 199 (23%) pts had at least one PLPV in a hereditary cancer susceptibility gene, while 253 (29.3%) had a variant of uncertain significance. Of 630 CRC pts, 24% had a PLPV and 13% harbored a germline mutation in DNA MMR genes and were diagnosed with Lynch Syndrome, representing ~50% of all pts with a PLPV. Other germline PLPVs were found in APC, ATM, BRCA1, BRCA2, CHEK2, MUTYH, and PALB2. Of 163 PC pts, 16.6% had a PLPV in ATM, BRCA2, CDKN2A, and MEN1. Gastric cancer pts (17%) had germline PLPVs in APC, BRCA2, CDH1, MLH1, and MSH2; biliary cancer pts (17%) had germline PLPVs in PALB2, RAD50, and PTCH1; and GIST pts (60%) had PLPVs in SDHA or SDHB. Conclusions: Germline mutations were found in 23% of GI cancer pts, underlining the importance of multigene germline testing. Knowledge of inherited GI cancer risk helps determine the likelihood of benefit from possible specific targeted therapies. Genetic testing and counseling pose a challenge, but implications for pts with hereditary syndromes are highly significant. [Table: see text]

scholarly journals Elucidating the phenotypic variability associated with the polyT tract and TG repeats in CFTR

2020 ◽  
Author(s):  
Keith Nykamp ◽  
Rebecca Truty ◽  
Darlene Riethmaier ◽  
Julia Wilkinson ◽  
Sara L. Bristow ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Family History ◽  
Hereditary Cancer ◽  
Phenotypic Variability ◽  
Clinical Information ◽  
History Of ◽  
Disease Risks ◽  
Reduced Penetrance ◽  
The Individual ◽  
Single Organ

ABSTRACTPurposeTo evaluate the risk and spectrum of phenotypes associated in individuals with one or two of the CFTR T5 haplotype variants (TG11T5, TG12T5 and TG13T5) in the absence of the R117H variant.MethodsIndividuals who received testing with CFTR NGS results between 2014 and 2019 through Invitae at ordering provider discretion were included. TG-T repeats were detected using a custom-developed haplotype caller. Frequencies of the TG-T5 variants (biallelic or in combination with another CF-causing variant [CFvar]) were calculated. Clinical information reported by the ordering provider (via requisition form) or the individual (during genetic counseling appointments) was examined.ResultsAmong 548,300 individuals, the minor allele frequency of the T5 allele was 4.2% (TG repeat distribution: TG11=68.1%, TG12=29.5%, TG13=2.4%). When present with a CFvar, each of the TG[11-13]T5 variants were significantly enriched in individuals with a “high suspicion” of CF/CFTR-RD (personal/family history of CF/CFTR-RD) compared to those with very “low suspicion” for CF or CFTR-RD (hereditary cancer testing, CFTR not requisitioned). Compared to CFvar/CFvar individuals, TG[11-13]T5/CFvar individuals generally had single organ involvement, milder symptoms, variable expressivity, and reduced penetrance.DiscussionData from this study provides a better understanding of disease risks associated with inheriting TG[11-13]T5 variants and has important implications for reproductive genetic counseling.

Germline mutations in cancer predisposition genes among patients with thyroid cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1581-1581
Author(s):  
Junne Kamihara ◽  
Holly LaDuca ◽  
Emily Dalton ◽  
Virginia Speare ◽  
Judy Ellen Garber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Thyroid Cancer ◽  
Hereditary Cancer ◽  
Clinical History ◽  
Germline Mutations ◽  
Cancer Predisposition ◽  
High Rate ◽  
Degree Relative ◽  
Clinical Genetic ◽  
History Of

1581 Background: Thyroid cancers are known component tumors of both well-described and emerging hereditary cancer syndromes. To assess the contribution of germline variants in thyroid cancer predisposition, we examined the prevalence of germline mutations among individuals with a history of thyroid cancer, compared to those with thyroid and breast cancer or breast cancer alone. Methods: Clinical histories and molecular results were reviewed for individuals with a history of thyroid and/or breast cancer, ascertained from a cohort of > 140,000 patients who underwent hereditary cancer multigene panel testing at a single commercial laboratory. Clinical history information was obtained from test requisition forms completed by ordering clinicians and from pedigrees/clinic notes, if provided. Results: Among 2,678 thyroid cancer patients, the majority were Caucasian (66.9%), female (92.3%), and/or had an additional cancer primary (71.9%), with nearly half reporting an additional breast cancer primary (49.1%). Among those with available pathology information, 4.1% had medullary thyroid cancer. The median (IQR) age at diagnosis was 38 (26,48) years, and while 94.1% had a family history of cancer, 78.8% had at least one affected 1st degree relative. Overall, 11.1% were identified as mutation carriers, defined as ≥1 pathogenic or likely pathogenic variant. Among those with thyroid cancer alone, 9.7% had a mutation, similar to those with breast cancer alone (9.7%) and those with breast and thyroid cancer only (10.5%). Genes most frequently mutated in the thyroid only group included CHEK2 (3.1%), MUTYH (monoallelic) (2.4%), APC (2.0%), ATM (1.6%), and PALB2 (1.2%). CHEK2 was the most frequently mutated gene observed in all groups, with a higher frequency seen among those with thyroid and breast cancer (5.5%) compared to breast cancer (2.5%) or thyroid cancer (3.1%) alone (p < 0.001). Conclusions: A high rate of germline mutations is observed among individuals with thyroid cancer presenting for clinical genetic testing, even in the absence of other primary cancer diagnoses. Thyroid cancer may be an under-recognized component tumor of hereditary cancer predisposition syndromes suggesting the need for further investigation.

The prevalence of germline mutations among patients with solid tumors with genomic alterations identified on tumor testing: Results from a tertiary care academic center molecular tumor board.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1516-1516
Author(s):  
Catherine Watson ◽  
Sarah Tait ◽  
Lindsay Soo ◽  
Jennifer Kay Plichta ◽  
Tian Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Germline Mutation ◽  
Tertiary Care ◽  
Retrospective Chart Review ◽  
Germline Mutations ◽  
Tumor Board ◽  
Genomic Alteration ◽  
Genomic Alterations ◽  
Academic Center ◽  
Germline Testing

1516 Background: The proportion of germline versus somatic mutations identified on genomic tumor testing of solid malignancies is not well characterized. We compared somatic and germline testing results in patients with breast, ovarian, pancreatic or prostate cancer with a genomic alteration identified on tumor testing. Methods: Retrospective chart review was performed using a tertiary care academic center’s database of somatic tumor testing results obtained via FoundationOne and Guardant testing. Patients with breast, ovarian, pancreatic or prostate cancer who had a genomic alteration identified on tumor testing, including pathogenic and VUS variants, in BRCA1or BRCA2, CHEK2, ATM, BRIP1, RAD51C, RAD51D, PALB2and CDH1and who had also received germline testing were identified. Analysis was performed to assess prevalence of germline results. The association between mutant allele fraction (MAF) and germline mutation status was also assessed. Results: Results: 124 patients with breast, ovarian, pancreatic or prostate cancer were identified who had a genomic alteration of interest also tested for via germline testing. 54 (32.5%) of tumor mutations were also identified on germline testing. Proportion of genomic results that were germline was wide, ranging from 0-85.7% depending on the gene and variant classification (Table). Germline mutations were present in 36.4% of breast, 25% of ovarian, 53.3% of pancreatic, and 20.9% of prostate cancer patients who had a tumor alteration present. Alterations that were found to be concordant in both somatic and germline testing had an average MAF of 0.54, and alterations identified on somatic testing only had an average MAF of 0.30. Conclusions: Our findings suggest that approximately one-third of genomic alterations on tumor testing will be of germline origin. However, concordance rates may be gene and variant dependent. Higher MAF may be associated with germline alteration status, but further evaluation is needed. Thus, while information provided by genomic tumor testing may be suggestive of a correlating germline mutation, no single alteration type or MAF value is reliably predictive. [Table: see text]

Improving the referral rate of universal genetic counseling for pancreatic ductal adenocarcinoma (PDAC) at the Cleveland Clinic Taussig Cancer Center: A quality improvement project.

2020 ◽  
Vol 38 (29_suppl) ◽  
pp. 196-196
Author(s):  
Kanika G. Nair ◽  
Brandie Leach ◽  
Selina Sledge ◽  
Megan Kilbane ◽  
Jennifer Bates ◽  
...  
Keyword(s):  
Quality Improvement ◽  
Genetic Counseling ◽  
Patient Education ◽  
Germline Mutations ◽  
Referral Rate ◽  
Quality Improvement Project ◽  
Tumor Board ◽  
Improvement Project ◽  
Referral Rates ◽  
Germline Testing

196 Background: While most PDAC are sporadic, up to 10% are inherited. In 2018, ASCO and NCCN guidelines were updated to recommend that all patients with PDAC be considered for genetic counseling (GC) and germline testing. Furthermore, interest in treating patients with targeted therapy, such as olaparib, for germline mutations is increasing. We implemented a quality improvement project to identify the referral rate to GC for patients with PDAC, with the goal of improving the referral rate to 60%. Methods: Barriers to GC referral were identified using quality improvement tools developed at the ASCO Quality Training Program. Three “plan, do, study, act” (PDSA) cycles were implemented: 1) updating the electronic order and tumor board template to include GC recommendation (Aug–Oct 2019), 2) physician education (Nov–Dec 2019) and 3) patient education and physician reinforcement (Jan–Feb 2020). Baseline data to evaluate impact of PDSA intervention (from April to June 2019) on documented discussions about GC and placement of the referral order was completed via chart review. Results: Between April 2019 to January 2020, 199 patients with PDAC were seen in medical oncology clinic as new patient visits. Thirteen patients had previously completed GC. For the remainder, baseline discussion and referral rates were 25% and 9%, respectively. Discussion and referral rates improved to 55% and 30% after PDSA 1, to 73% and 33% after PDSA 2, and to 95% and 58% after PDSA 3, respectively. Forty-nine patients were referred at the first visit and 23 were referred at a subsequent visit. Forty-six patients underwent GC. In patients who completed germline testing 8.9% (4/45) were found to have a pathogenic variant in BRCA2, TP53, ATM, and MUTYH. Conclusions: With increased physician and patient education, we were able to improve the GC discussion rate from 25% to 95% and referral rate from 9% to 58%. While we did not meet our aim of 60% GC referral rate, we identified obstacles and outlined an improved process for early GC referrals. Enacting processes to reinforce GC referrals for patients with PDAC is likely to increase detection of germline mutations in this population.

scholarly journals High Prevalence of Hereditary Cancer Syndromes in Adolescents and Young Adults With Colorectal Cancer

2015 ◽  
Vol 33 (31) ◽  
pp. 3544-3549 ◽  
Author(s):  
Maureen E. Mork ◽  
Y. Nancy You ◽  
Jun Ying ◽  
Sarah A. Bannon ◽  
Patrick M. Lynch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Genetic Counseling ◽  
Family History ◽  
Hereditary Cancer ◽  
Hereditary Cancer Syndrome ◽  
Hereditary Cancer Syndromes ◽  
Cancer Syndrome ◽  
History Of ◽  
Cancer Syndromes ◽  
History Of Cancer

Purpose Established guidelines recommend evaluation for hereditary cancer syndromes in patients younger than 50 years diagnosed with colorectal cancer (CRC). This group has been well described in the literature; however, patients diagnosed as adolescents and young adults are not well represented in CRC studies. Here, we define the clinical profile, including the extent of hereditary cancer syndromes and family history of cancer, in patients diagnosed with CRC at age 35 or younger. Patients and Methods We reviewed patients who underwent genetic counseling at our institution during 5 years (2009 to 2013). Data were collected regarding demographics, clinicopathologic information, tumor and genetic testing, and family history. Patients with an identified hereditary cancer syndrome were compared with those without a syndrome. Results Of the 193 patients with evaluable data, 35% had an identifiable hereditary cancer syndrome, including 23 with Lynch syndrome, 22 with mutation-negative Lynch syndrome, 16 with familial adenomatous polyposis, two with constitutional mismatch repair deficiency, two with biallelic MUTYH mutations, and one with Li-Fraumeni syndrome. Patients without a hereditary syndrome more frequently presented with metastatic disease, whereas patients with a syndrome were more likely to present at earlier stages and to have a family history of cancer. Nevertheless, a substantial proportion of the hereditary syndromes (19%) were diagnosed in individuals with no family history of the disease. Conclusion We conclude that patients diagnosed with CRC at age 35 years or younger should receive genetic counseling regardless of their family history and phenotype.

Germline testing of patients with personal history of colorectal polyposis by cancer genetics counseling services.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 47-47
Author(s):  
Gideon T Dosunmu ◽  
Cassandra Gurganus ◽  
Veena Krishnan ◽  
Delmer Alfredo Montoya Motino ◽  
Sana Ozair ◽  
...  
Keyword(s):  
Cancer Genetics ◽  
Germline Mutations ◽  
Colorectal Polyps ◽  
Personal History ◽  
Counseling Services ◽  
Polyposis Syndrome ◽  
Hamartomatous Polyps ◽  
Colorectal Polyposis ◽  
History Of ◽  
Germline Testing

47 Background: National Comprehensive Cancer Network (NCCN) guidelines recommend that individuals with >10 adenomatous polyps, ≥2 hamartomatous polyps, or ≥5 serrated polyps proximal to the sigmoid colon have detailed risk assessment and potential genetic testing to rule out polyposis syndrome. Here, we describe germline testing of patients with a personal history of colorectal polyposis by Cancer Genetics Counseling Services. Methods: This is an IRB-approved retrospective chart-review study. Between 2016 and 2020, 1011 unique genetic counseling visits were conducted. Germline testing was recommended by a certified genetic counselor if medically necessary. All patients with a personal history of colorectal polyposis were identified (N=20) and their germline testing results were summarized. Results: The reasons for referral to the Cancer Genetics Counseling Services were personal history of >10 adenomatous polyps (N=13), personal and family history of colorectal polyposis (N=3), personal history of juvenile colorectal polyps (N=3) or personal history of ≥2 hamartomatous polyps (N=1). The median age is 58 years-old (1-84). Ten (50%) patients were females. Caucasians, African Americans and other ethnic backgrounds represented 80%, 10% and 10% respectively. In our cohort, 6 out of 20 (30%) patients had a pathogenic germline mutation, 5 (25%) patients had variant of unknown significance (VUS) and 9 (45%) patients had negative testing. Among patients with pathogenic germline mutations, 3 patients had a pathogenic APC mutation (APC c.1659G>A, APC c.2802C>A and APC c.1643dupT) and were diagnosed with Familial Adenomatous Polyposis (FAP). One patient had 2 pathogenic MUTYH mutations (MUTYH c.536A>G and MUTYH c.1187G>A) and was diagnosed with One patient had a pathogenic PTEN c.634+5G>A mutation and was diagnosed with PTEN Hamartoma Tumor Syndrome. Among the 3 patients with a personal history of juvenile colorectal polyps, one patient had a CHEK2 c.190G>A mutation while the other two had negative genetic test results. The VUS mutations in our cohort were MRE11A c.826C>T, BLM c.3478T>C, BRCA2 c.2519T>C, CHEK2 p.V395L and CTNNA1 c.392dupT. Conclusions: In our cohort of patients with personal history of colorectal polyposis, the majority of patients (45%) had negative germline testing. An underlying pathogenic germline mutation and VUS were identified in 30% and 25% of the patients, respectively. FAP Syndrome was the most commonly diagnosed hereditary polyposis syndrome with 3 patients found to have APC germline mutations. Other pathogenic mutations were identified in the MUTYH, PTEN and CHEK2 genes. Patients with MUTYH and PTEN mutations were diagnosed with MAP and PTEN Hamartoma Tumor Syndromes respectively.

The clinical and molecular characteristics of patients with personal history of colorectal cancer evaluated by cancer genetics counseling services.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 46-46
Author(s):  
Veena Krishnan ◽  
Cassandra Gurganus ◽  
Delmer Alfredo Montoya Motino ◽  
Gideon T Dosunmu ◽  
Sana Ozair ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Cancer Genetics ◽  
Germline Mutations ◽  
Personal History ◽  
Molecular Characteristics ◽  
Counseling Services ◽  
Polyposis Syndrome ◽  
History Of ◽  
Germline Testing

46 Background: Genetic susceptibility to colorectal cancer (CRC) include well-defined hereditary syndromes such as Lynch Syndrome, Familial Adenomatous Polyposis syndrome (FAP), MUTYH-Associated Polyposis syndrome (MAP) and other less common syndromes. National Comprehensive Cancer Network (NCCN) guidelines recommend that individuals meeting certain criteria have detailed risk assessment and potential genetic testing. Here, we describe the clinical and molecular characteristics of patients with personal history of CRC evaluated by cancer genetics counseling services. Methods: This is an IRB-approved retrospective chart-review study. Between 2016 and 2020, 1011 unique genetic counseling visits were conducted. Germline testing was recommended by a certified genetic counselor if medically necessary. All patients with a personal history of CRC were identified (N = 52) and their clinical and molecular characteristics were summarized. Results: The median age is 50 years-old (29-82). Thirty-five (67%) patients were females. Caucasians, African Americans and other ethnic backgrounds represented 75%, 19% and 6% respectively. The primary tumor location was in the right colon, left colon and rectum in 29%, 37% and 27% of our cohort respectively. In 7%, the primary location of the tumor was not available. In our cohort, 11 out of 52 (21%) patients had a pathogenic germline mutation and 9 patients (17%) had a germline variant of unknown significance (VUS). Among patients with pathogenic germline mutations (N = 11), 4 patients had MSH2 mutations (MSH2 c.1759+1G > A, MSH2 c. 1687dupT, MSH2 c.1861C > T and MSH2 c.811_814delTCTG), 1 patient had a MSH6 mutation (MSH6 c.1012A > T), 1 patient had a PMS2 mutation (PMS2 c.2182_2184delACTinsG), 3 patients had CHEK2 mutations (CHEK2 c.1100delC and CHEK2 c.470T > C (p.I157T)), 2 patients had MUTYH mutations (MUTYH c.1187G > A and MUTYH c.536A > G) and 1 patient had a BRCA2 mutation (BRCA2 c.2808_2811delACAA). One patient had a CHEK2 and a MUTYH mutation. The VUS mutations in our cohort were POLE c.1645T > C, POLE c.5480C > T, c.2999G > A, MLH1 c.1628A > G, CTNNA1 c.503G > A, MSH2 c.128A > G, NBN c.16C > T, ATM c.6537T > G and AXIN2, BRCA1, NTHL1 mutations. Conclusions: In our cohort of patients with personal history of CRC, the majority of patients (62%) had negative germline testing. An underlying pathogenic germline mutation and VUS were identified in 21% and 17% of the patients respectively. Lynch Syndrome was the most commonly diagnosed hereditary CRC syndrome with 6 out of 11 patients found to have MMR germline mutations. Other pathogenic mutations were identified in the CHEK2, MUTYH and BRCA2 genes.

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