Rare Germline Variants in DNA Repair Genes Detected in BRCA-Negative Finnish Patients with Early-Onset Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Turku Whole-Exome Sequencing Set
2.1.1. Study Subjects
2.1.2. Sample Preparation and Whole-Exome Sequencing
2.1.3. Data Analysis
2.1.4. Variant Filtering
2.2. Validation Set Helsinki
2.3. Protein Structure Modeling
3. Results
3.1. Turku Whole-Exome Sequencing Set Results
3.2. Validation Set Helsinki Results
3.3. Protein Structure Modeling of Novel Variants
4. Discussion
4.1. Novel Variants Detected
4.2. Previously Known Cancer Variants Detected
4.3. Polygenic Variants Detected
4.4. The Homogenic Group of the Study’s EOBC Patients
4.5. Limitations of the Study
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
BC | Breast cancer |
DCIS | Ductal carcinoma in situ |
DSB | Double-strand break |
EOBC | Early-onset breast cancer |
ER | Estrogen receptor |
HER2 | Human epidermal growth factor receptor 2 |
LCIS | Lobular carcinoma in situ |
PR | Progesterone receptor |
PRS | Polygenic risk score |
PV | pathogenic variant |
TNBC | Triple-negative breast cancer |
VUS | Variant of unknown significance |
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Variant | Gene | Location | Nucleotide Change | Effect on Protein | Consequence | Subcategory | gnomADe FIN AF | gnomADg FIN AF | SIFT | PolyPhen | REVEL | CADD PHRED |
---|---|---|---|---|---|---|---|---|---|---|---|---|
rs193219754 | MLH3 | chr14:75039918 | c.3563C>G | p.Ser1188Ter | stop gained | 0.002491 | 0.003159 | NA | NA | NA | 42 | |
rs180177100 | PALB2 | chr16:23635306 | c.1240C>T | p.Arg414Ter | stop gained | 0 | 0 | NA | NA | NA | 37 | |
rs11574410 | WRN | chr8:31173019 | c.4216C>T | p.Arg1406Ter | stop gained | 0.0006469 | 0.0002832 | NA | NA | NA | 36 | |
rs81002862 | BRCA2 | chr13:32380005 | c.9118-2A>G | NA | splice acceptor | 0.0003697 | 0.0001885 | NA | NA | NA | 35 | |
rs11571833 | BRCA2 | chr13:32398489 | c.9976A>T | p.Lys3326Ter | stop gained | 0.01086 | 0.01045 | NA | NA | NA | 35 | |
rs5745908 | NEIL1 | chr15:75349341 | c.434+2T>C | NA | splice donor | 0.0018 | 0.001508 | NA | NA | NA | 34 | |
rs587782401 | CHEK2 | chr22:28734401 | c.319+2T>A | NA | splice donor | 0.0005548 | 0.0003764 | NA | NA | NA | 34 | |
rs766240074 | RAD54L | chr1:46273748 | c.1610+1G>A | NA | splice donor | 4.968 × 10−5 | 0 | NA | NA | NA | 33 | |
chr4:2490336 G/T | RNF4 | chr4:2490336 | c.-157-1G>T | NA | splice acceptor | NA | NA | NA | NA | NA | 33 | |
rs756188698 | RAD18 | chr3:8899048 | c.1169-1G>C | NA | splice acceptor | 0.0002398 | 9.457 × 10−5 | NA | NA | NA | 28.9 | |
rs11572913 | GTF2H3 | chr12:123633862 | c.3G>A | p.Met1? | start lost | 0.0007112 | 0.000565 | 0.02lc | 0.273 | NA | 24.8 | |
rs187418762 | SPIDR | chr8:47713484 | c.2189-5G>A | NA | splice region, splice polypyrimidine tract, intron | 0.01286 | 0.01198 | NA | NA | NA | 20.5 | |
rs149243307 | FANCI | chr15:89260841 | c.286G>A | p.Glu96Lys | missense, splice region | 2 | 0.001848 | 0.001507 | 0 | 1 | 0.448 | 33 |
rs41540016 | POLQ | chr3:121436275 | c.7390G>A | p.Ala2464Thr | missense, splice region | 2 | 0.01381 | 0.01208 | 0 | 1 | 0.84 | 33 |
chr1:241861448 -/T | EXO1 | chr1:241861447-241861448 | c.987dup | p.Lys330Ter | frameshift | 1 | NA | NA | NA | NA | NA | 33 |
rs773570504 | ATM | chr11:108326152-108326153 | c.6908dup | p.Glu2304GlyfsTer69 | frameshift | 1 | 4.625 × 10−5 | 9.56 × 10−5 | NA | NA | NA | 33 |
rs762390984 | FANCI | chr15:89301393-89301405 | c.2957_2969del | p.Val986AlafsTer39 | frameshift | 1 | 0.002957 | 0.002454 | NA | NA | NA | 33 |
rs759217526 | FANCL | chr2:58159793-58159794 | c.1096_1099dup | p.Thr367AsnfsTer13 | frameshift | 1 | 0.001814 | 0.002649 | NA | NA | NA | 33 |
rs199791286 | MSH3 | chr5:80778737 | c.2336G>A | p.Arg779His | missense | 1 | 0.001294 | 0.001415 | 0 | 1 | 0.884 | 32 |
chr8:31111721 G/C | WRN | chr8:31111721 | c.2195G>C | p.Arg732Pro | missense | 2 | NA | NA | 0 | 1 | 0.499 | 31 |
chr12:132677395 -/T | POLE | chr12:132677394-132677395 | c.769dup | p.Ile257AsnfsTer6 | frameshift | 1 | NA | NA | NA | NA | NA | 31 |
rs28363284 | RAD51D | chr17:35103294 | c.698A>G | p.Glu233Gly | missense | 1 | 0.001185 | 0.001797 | 0.04 | 0.973 | NA | 29.9 |
rs746243211 | MSH3 | chr5:80672754 | c.923A>T | p.Lys308Met | missense | 1 | 0 | 0 | 0 | 1 | 0.823 | 29.7 |
rs137923123 | PER1 | chr17:8147713 | c.1349G>A | p.Arg450His | missense | 1 | 0.003681 | 0.002823 | 0 | 1 | NA | 29.2 |
rs373080718 | TOP3A | chr17:18277728 | c.2774C>T | p.Pro925Leu | missense | 1 | 4.623 × 10−5 | 0 | 0.01 | 0.999 | NA | 29 |
rs2306211 | POLQ | chr3:121432937 | c.7640C>T | p.Ala2547Val | missense | 2 | 0.007347 | 0.006223 | 0.03 | 1 | 0.571 | 28.8 |
rs200535477 | RECQL5 | chr17:75627670 | c.2828G>A | p.Arg943His | missense | 1 | 0.009798 | 0.008201 | 0 | 1 | NA | 28.7 |
rs202068855 | RPA1 | chr17:1880615 | c.1165C>T | p.Arg389Trp | missense | 2 | 0.01502 | 0.0152 | 0 | 1 | NA | 28.1 |
rs144564120 | ERCC2 | chr19:45352249 | c.2150C>G | p.Ala717Gly | missense | 1 | 4.624 × 10−5 | 0 | 0.01 | 0.015 | NA | 28.1 |
rs28897758 | BRCA2 | chr13:32394734 | c.1267T>G | p.Cys423Gly | missense | 1 | 0.0004619 | 0.000659 | 0 | 1 | 0.788 | 28 |
rs34001746 | TOP3A | chr17:18285268 | c.1751T>G | p.Leu584Arg | missense | 1 | 0.0004619 | 0.000659 | 0.02 | 0.803 | NA | 27.3 |
rs121913016 | ERCC2 | chr19:45357368 | c.1381C>G | p.Leu461Val | missense | 1 | 4.633e-05 | 0 | 0 | 0.982 | NA | 27.3 |
rs1805378 | NTHL1 | chr16:2044652 | c.503T>C | p.Ile168Thr | missense | 1 | 0.0004352 | 0.0003766 | 0 | 1 | 0.876 | 27.1 |
rs34642881 | RECQL4 | chr8:144517415 | c.212A>G | p.Glu71Gly | missense, splice region | 1 | 0.004511 | 0.005941 | 0.02 | 0.803 | NA | 26.6 |
rs17879961 | CHEK2 | chr22:28725099 | c.470T>C | p.Ile157Thr | missense | 1 | 0.004511 | 0.005941 | 0.07 | 0.514 | NA | 26.5 |
rs142213781 | NEIL1 | chr15:75353853 | c.833C>T | p.Thr278Ile | missense | 2 | 0.002086 | 0.002352 | 0 | 1 | 0.563 | 26.4 |
rs562132292 | ERCC2 | chr19:45357290 | c.1459C>T | p.Arg487Trp | missense | 1 | 0.0003272 | 0.0006591 | 0 | 0.998 | NA | 26.4 |
chr6:37360499 C/G | RNF8 | chr6:37360499 | c.165C>G | p.Cys55Trp | missense | 2 | NA | NA | 0 | 1 | 0.747 | 26.3 |
rs149253459 | FAAP100 | chr17:81547649 | c.1433A>G | p.Gln478Arg | missense | 1 | 0.002894 | 0.0016 | 0.01 | 0.997 | NA | 26.2 |
rs750771205 | ATM | chr11:108289000 | c.4133C>T | p.Pro1378Leu | missense | 2 | 0 | 0 | 0 | 0.969 | 0.546 | 26.1 |
rs1801673 | ATM | chr11:108304736 | c.5558A>T | p.Asp1853Val | missense | 2 | 0.003699 | 0.00292 | 0 | 0.987 | 0.589 | 26.1 |
rs1799802 | ERCC4 | chr16:13934224 | c.1135C>T | p.Pro379Ser | missense | 2 | 0.007207 | 0.009714 | 0 | 1 | 0.526 | 25.4 |
rs11212587 | ATM | chr11:108315883 | c.6067G>A | p.Gly2023Arg | missense | 2 | 0.0008318 | 0.0007553 | 0 | 0.364 | 0.511 | 25.3 |
rs61752784 | POLG | chr15:89330133 | c.803G>C | p.Gly268Ala | missense | 1 | 0.004158 | 0.00546 | 0 | 0.999 | 0.967 | 25.3 |
rs200981995 | LIG3 | chr17:34999827 | c.2302T>C | p.Tyr768His | missense | 2 | 0.01173 | 0.009134 | 0.11 | 0.994 | NA | 25.1 |
chr17:18292743 T/A | TOP3A | chr17:18292743 | c.1183A>T | p.Ser395Cys | missense | 1 | NA | NA | 0.01 | 0.976 | NA | 25 |
rs201920810 | SPIDR | chr8:47712713 | c.2029G>A | p.Asp677Asn | missense | 2 | 0 | 0 | 0 | 1 | 0.561 | 24.9 |
rs140566004 | POLE | chr12:132673646 | c.1288G>A | p.Ala430Thr | missense | 2 | 0.0001395 | 0 | 0 | 0.997 | 0.487 | 24.7 |
rs78488552 | WRN | chr8:31154721 | c.3785C>G | p.Thr1262Arg | missense | 2 | 0.000231 | 9.432 × 10−5 | 0 | 0.999 | 0.413 | 24.5 |
rs546221341 | POLQ | chr3:121488663-121488669 | c.4262_4268del | p.Ile1421ArgfsTer8 | frameshift | 1 | 0.006209 | 0.005384 | NA | NA | NA | 24.3 |
rs145289229 | POLG | chr15:89328532 | c.1174C>G | p.Leu392Val | missense | 1 | 0.007823 | 0.01085 | 0.06 | 0.999 | 0.796 | 24.2 |
rs55748151 | POLQ | chr3:121533021 | c.929T>G | p.Val310Gly | missense | 2 | 0.001063 | 0.001413 | 0 | 0.552 | 0.498 | 24.1 |
rs150018949 | EXO5 | chr1:40515573-40515574 | c.1029_1030insG | p.Arg344AlafsTer10 | frameshift | 1 | 0.004352 | 0.003488 | NA | NA | NA | 24.1 |
rs771308001 | ERCC1 | chr19:45407145-45407146 | NA | NA | downstream gene | 1 | 0.003376 | 0.00311 | NA | NA | NA | 23.7 |
rs565251228 | RECQL5 | chr17:75624891 | NA | NA | downstream gene | 1 | 0.0001461 | 0.0002827 | NA | NA | NA | 23.4 |
rs55801750 | ATM | chr11:108330296 | c.7390T>C | p.Cys2464Arg | missense | 2 | 4.619 × 10−5 | 0 | 0.1 | 0.005 | 0.668 | 22.9 |
rs201503405 | PNKP | chr19:49862573 | c.901C>T | p.Arg301Trp | missense | 1 | 0.006464 | 0.006775 | 0 | 0.911 | NA | 22.9 |
chr19:45352306 T/C | ERCC2 | chr19:45352306 | c.2093A>G | p.Gln698Arg | missense | 1 | NA | NA | 0.54 | 0.218 | NA | 22.8 |
chrX:153444976 C/G | TREX2 | chrX:153444976 | c.455G>C | p.Arg152Pro | missense | 1 | NA | NA | 0 | 0.999 | NA | 22.7 |
rs775001669 | MLH3 | chr14:75048767 | c.889C>T | p.Arg297Trp | missense | 2 | 0.00134 | 0.001132 | 0 | 1 | 0.655 | 22.6 |
rs41549716 | POLG | chr15:89321842 | c.2492A>G | p.Tyr831Cys | missense | 2 | 0.01803 | 0.0161 | 0.02 | 0.995 | 0.732 | 22.6 |
rs201414369 | EME1 | chr17:50380824 | c.1598G>A | p.Arg533His | missense | 1 | 0.0001386 | 0.0001884 | 0.22 | 0.994 | NA | 22.6 |
rs144340710 | TP53 | chr17:7674259 | c.704A>G | p.Asn235Ser | missense | 1 | 0.0002772 | 0.0004745 | 0.22 | 0.385 | NA | 22.5 |
rs4987202 | RAD23A | chr19:12948812 | c.599C>T | p.Thr200Met | missense, splice region | 1 | 0.004359 | 0.003299 | 0.43 | 0.02 | NA | 22.5 |
rs146309259 | LIG1 | chr19:48121298 | c.2257G>A | p.Val753Met | missense | 1 | 0.002451 | 0.001788 | 0.06 | 0.407 | NA | 22.5 |
rs28897689 | BRCA1 | chr17:43091492 | c.4039A>G | p.Arg1347Gly | missense | 1 | 0.001944 | 0.001788 | 0.09 | 0.255 | NA | 22.2 |
rs55712212 | BRCA2 | chr13:32341176 | c.6821G>T | p.Gly2274Val | missense | 2 | 0.01303 | 0.01349 | 0.37 | 0.966 | 0.481 | 21.8 |
rs144276604 | XAB2 | chr19:7625912 | c.790G>A | p.Asp264Asn | missense | 1 | 0.0002318 | 0 | 0.09 | 0.846 | NA | 21.7 |
rs3730947 | LIG1 | chr19:48140013 | c.1045G>A | p.Val349Met | missense | 2 | 0.01564 | 0.01648 | 0 | 0.997 | NA | 21.5 |
rs776329282 | ERCC4 | chr16:13926750-13926755 | c.580_584+1del | NA | in-frame deletion, splice region | 1 | 9.256 × 10−5 | 0.0001884 | NA | NA | NA | 20.5 |
rs763165669 | NTHL1 | chr16:2038404-2038416 | NA | NA | downstream gene | 2 | 0.01363 | 0.007775 | NA | NA | NA | NA |
rs41547220 | POLQ | chr3:121489857-121489859 | c.3072_3074del | p.Lys1025del | in-frame deletion | 2 | 0.01831 | 0.01925 | NA | NA | NA | NA |
ID* | Found var | Age | Histology, Grade, ER, PR, Her2 | ||||
---|---|---|---|---|---|---|---|
424 | rs145289229 | rs11571833 | rs2306211 | rs546221341 | 25 | Ductal, G3, ER+, PR-, Her2+ | |
POLG | BRCA2 | POLQ | POLQ | ||||
425 | 27 | Ductal, G3, ER+, PR+, Her2- | |||||
426 | 27 | Ductal, G3, ER-, PR-, NA | |||||
427 | 28 | Ductal, G3, ER+, PR+, Her2+ | |||||
428 | rs11571833 | rs3730947 | 28 | Ductal, G3, ER-, PR-, Her2- | |||
BRCA2 | LIG1 | ||||||
429 | 28 | Ductal, G3, ER+, PR+, Her2+ | |||||
431 | rs140566004 | rs4987202 | 28 | Ductal, G3, ER-, PR+, Her2+ | |||
POLE | RAD23A | ||||||
432- | rs201920810 | rs773570504 | 30 | Ductal, G3, ER+, PR+, Her2- | |||
SPIDR | ATM | ||||||
433 | 31, 35 | Ductal, G3, ER-, PR-, Her2-; 2 Ductal, ER+, Her2- ^ | |||||
434- | rs200535477 | rs2306211 | 31 | Ductal, G3, ER-, PR-, Her2- | |||
RECQL5 | POLQ | ||||||
435- | Novel RNF8 | rs78488552 | rs565251228 | 32 | Ductal, G3, ER-, PR-, Her2+ | ||
WRN | RECQL5 | ||||||
436- | rs1801673 | rs762390984 | rs763165669 | 32 | Micropapillar, ER+, PR+, Her2- | ||
ATM | FANCI | NTHL1 | |||||
437 | rs373080718 | rs202068855 | 33 | DCIS, G3 | |||
TOP3A | RPA1 | ||||||
438- | rs187418762 | 33 | Ductal, G3, ER-, PR-, Her2- | ||||
SPIDR | |||||||
440 | rs55712212 | rs137923123 | novel ERCC2 | 34, 37 | Ductal, G3, ER-, PR-; 2 LCIS | ||
BRCA2 | PER1 | ||||||
441- | 34 | Ductal, G3, ER+, PR+, Her2- | |||||
442 | rs41547220 | rs149253459 | 34 | Ductal, G3, ER+, PR+, Her2- | |||
POLQ | FAAP100 | ||||||
443- | rs766240074 | rs562132292 | 34 | Ductal, G3, ER-, PR-, Her2- | |||
RAD54L | ERCC2 | ||||||
444- | 35 | Ductal, G3, ER-, PR-, Her2+ | |||||
445 | rs587782401 | 35,43 | Ductal, G3, ER-, PR-, Her2+; 2 Ductal, G3, ER-, PR-, Her2+ | ||||
CHEK2 | |||||||
446- | rs771308001 | 34 | Ductal, G2, ER+, PR+, Her2- | ||||
ERCC1 | |||||||
610 | rs28897758 | rs1805378 | 40, 40 | Ductal, G1, ER+, PR+, Her2-; 2 G3, ER+, PR+, Her2- | |||
BRCA2 | NTHL1 | ||||||
611 | 40, 54 | Ductal, G2, ER+, PR-, Her2-; 2 ductal, G2, ER+, PR+, Her2- | |||||
612 | rs81002862 | rs11212587 | 40 | DCIS | |||
BRCA2 | ATM | ||||||
613 | 35 | ||||||
614 | 26 | DCIS, G3 | |||||
615 | rs55748151 | 30 | Ductal, G3, ER-, PR-, Her2- | ||||
POLQ | |||||||
616 | rs55801750 | rs34001746 | rs144276604 | 38 | Ductal, G3, ER-, PR-, Her2+ | ||
ATM | TOP3A | XAB2 | |||||
617 | rs746243211 | Novel Trex2 | 40, 67 | 2 Ductal G3, ER+, PR+, Her2- | |||
MSH3 | |||||||
618 | rs776329282 | 27 | Ductal, G2, ER+, PR+, Her2- | ||||
ERCC4 | |||||||
619 | rs5745908 | rs41549716 | Novel Top3A | rs41540016 | 27 | Ductal, G3, ER-, PR-, Her2- | |
NEIL1 | POLG | POLQ | |||||
61 | rs121913016 | rs180177100 | rs144564120 | 36 | Ductal, ER+, PR+, Her2- | ||
ERCC2 | PALB2 | ERCC2 | |||||
620 | 35 | Ductal, G2, ER+, PR+, Her2- | |||||
621 | rs55712212 | 39 | Lobular | ||||
BRCA2 | |||||||
622 | 38 | Ductal, G2, ER+, PR+, Her2+ | |||||
623 | Novel RNF4 | 31 | Ductal, G2, ER+, PR+, Her2+ | ||||
624 | rs149243307 | rs61752784 | rs17879961 | Novel EXO1 | 23 | Ductal, G3, ER+, PR+, Her2+ | |
FANCI | POLG | CHEK2 | |||||
625 | rs3730947 | 28 | Lobular, G2, ER+, PR+, Her2- | ||||
LIG1 | |||||||
626 | rs750771205 | rs145289229 | rs146309259 | rs3730947 | rs587782401 | 34, 34 | Ductal, ER+, PR+, Her2+; 2 DCIS |
ATM | POLG | LIG1 | LIG1 | CHEK2 | |||
627 | 33 | ||||||
628 | rs28363284 | rs41540016 | 28 | Ductal, G3, ER-, PR-, Her2- | |||
RAD51D | POLQ | ||||||
629- | rs150018949 | 40 | |||||
EXO5 | |||||||
62 | 36 | DCIS | |||||
630 | rs1799802 | 26 | Ductal, G3, ER-, PR-, Her2- | ||||
ERCC4 | |||||||
631- | rs193219754 | 31 | Ductal, G2, ER+, PR-, Her2- | ||||
MLH3 | |||||||
632 | rs187418762 | rs4987202 | rs201503405 | 38, 67 | Ductal; 2 ductal, G3, ER+, PR+, Her2- | ||
SPIDR | RAD23A | PNKP | |||||
633- | rs41540016 | 32 | Lobular, G2, ER+, PR+, Her2- | ||||
POLQ | |||||||
634- | Novel POLE | rs28897689 | Novel WRN | rs11574410 | 34 | Ductal, G3, ER-, PR-, Her2- | |
BRCA1 | WRN | ||||||
635- | rs144340710 | rs3730947 | 30 | Ductal, G3, ER+, PR-, Her2- | |||
TP53 | LIG1 | ||||||
636 | rs4987202 | 24 | |||||
RAD23A | |||||||
637 | rs150018949 | 31 | Ductal, G3, ER+, PR+, Her2+ | ||||
EXO5 | |||||||
639- | rs759217526 | 24 | Ductal, G3, ER+, PR+, Her2- | ||||
FANCL | |||||||
63 | rs11572913 | 37, 46 | Ductal, G2; 2 Ductal, G2, ER+, PR+, Her2- | ||||
GTF2H3 | |||||||
64 | 37, 57 | Ductal, G3, ER+, PR+, Her2-; 2 | |||||
65 | rs34642881 | 38 | |||||
RECQL4 | |||||||
66 | rs202068855 | rs756188698 | 39 | Ductal, G3, ER+, PR+, Her2- | |||
RPA1 | RAD18 | ||||||
67 | rs142213781 | 39 | Ductal, G1, ER+, PR+, Her2- | ||||
NEIL1 | |||||||
68 | 39, 47 | Lobular, G2, ER+, PR+, Her2-; 2 DCIS, G3 | |||||
69 | rs200981995 | rs17879961 | rs201503405 | 40 | Ductal, G3, ER-, PR-,Her2- | ||
LIG3 | CHEK2 | PNKP | |||||
71 | 29 | Ductal, G3, ER-, PR-, Her2- | |||||
72- | rs775001669 | rs41540016 | rs199791286 | 39 | Ductal, G3, ER+, PR+, Her2+ | ||
MLH3 | POLQ | MSH3 | |||||
73- | 33 | DCIS, G3 | |||||
74- | rs201414369 | rs150018949 | 36, 36 | Ductal, G3, ER-, PR-, Her2-; 2 ductal, G3, ER-, PR-, Her2- | |||
EME1 | EXO5 |
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Kurkilahti, V.; Rathinakannan, V.S.; Nynäs, E.; Goel, N.; Aittomäki, K.; Nevanlinna, H.; Fey, V.; Kankuri-Tammilehto, M.; Schleutker, J. Rare Germline Variants in DNA Repair Genes Detected in BRCA-Negative Finnish Patients with Early-Onset Breast Cancer. Cancers 2024, 16, 2955. https://doi.org/10.3390/cancers16172955
Kurkilahti V, Rathinakannan VS, Nynäs E, Goel N, Aittomäki K, Nevanlinna H, Fey V, Kankuri-Tammilehto M, Schleutker J. Rare Germline Variants in DNA Repair Genes Detected in BRCA-Negative Finnish Patients with Early-Onset Breast Cancer. Cancers. 2024; 16(17):2955. https://doi.org/10.3390/cancers16172955
Chicago/Turabian StyleKurkilahti, Viivi, Venkat Subramaniam Rathinakannan, Erja Nynäs, Neha Goel, Kristiina Aittomäki, Heli Nevanlinna, Vidal Fey, Minna Kankuri-Tammilehto, and Johanna Schleutker. 2024. "Rare Germline Variants in DNA Repair Genes Detected in BRCA-Negative Finnish Patients with Early-Onset Breast Cancer" Cancers 16, no. 17: 2955. https://doi.org/10.3390/cancers16172955